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Sample records for diazepam

  1. DRUG INTERACTIONS WITH DIAZEPAM

    Directory of Open Access Journals (Sweden)

    Zoran Bojanić

    2011-06-01

    Full Text Available Diazepam is a benzodiazepine derivative with anxyolitic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, antitremor, and amnestic activity. It is metabolized in the liver by the cytochrome P (CYP 450 enzyme system. Diazepam is N-demethylated by CYP3A4 and CYP2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyl-diazepam and temazepam are both further metabolized to oxazepam. Concomitant intake of inhibitors or inducers of the CYP isozymes involved in the biotransformation of diazepam may alter plasma concentrations of this drug, although this effect is unlikely to be associated with clinically relevant interactions.The goal of this article was to review the current literature on clinically relevant pharmacokinetic drug interactions with diazepam.A search of MEDLINE and EMBASE was conducted for original research and review articles published in English between January 1971. and May 2011. Among the search terms were drug interactions, diazepam, pharmacokinetics, drug metabolism, and cytochrome P450. Only articles published in peer-reviewed journals were included, and meeting abstracts were excluded. The reference lists of relevant articles were hand-searched for additional publications.Diazepam is substantially sorbed by the plastics in flexible containers, volume control set chambers, and tubings of intravenous administration sets. Manufacturers recommend not mixing with any other drug or solution in syringe or solution, although diazepam is compatible in syringe with cimetidine and ranitidine, and in Y-site with cisatracurium, dobutamine, fentanyl, hydromorphone, methadone, morphine, nafcillin, quinidine gluconate, remifentanil, and sufentanil. Diazepam is compatible with: dextrose 5% in water, Ringers injection, Ringers injection lactated and sodium chloride 0.9%. Emulsified diazepam is compatible with Intralipid and Nutralipid.Diazepam has low potential

  2. Deposition of diazepam and its metabolites in hair following a single dose of diazepam

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong

    2017-01-01

    Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy...... volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide...... no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were...

  3. Radiopharmaceutical potential of I-131 labelled diazepam

    International Nuclear Information System (INIS)

    Yurt, F.; Unek, P.; Asikoglu, M.; Baggi, S.; Erener, G.; Ozkilic, H.; Uluc, F.; Tuglular, I.

    1998-01-01

    In this study, diazepam is a derivative of the 1.4 benzodiazepine family that the most widely used drug as anticonvulsant agent has been labeled with I-131, as a new radiopharmaceutical and its radiopharmaceutical potential has been determined. Labeling of diazepam has been performed by iodogen method and optimum labeling conditions have been determined. Optimum reaction conditions are 1 mg for iodogen amount; 1-5 mg for diazepam amount, 15-20 minutes for reaction time and room temperature for reaction temperature. Specific activity of labeled compound was 0,15 Ci/mmol level. N-octanol/water ratio was found 1.9 for 131 IDZ ( 131 I labeled diazepam). In vivo experiments have been carried out to determine radiopharmaceutical potentials of labeled compound. Biodistribution studies on rats showed that 131 IDZ have accumulated in kidneys, liver, lungs and brain tissues. Scintigraphic results taken with gamma camera on rabbits agree with biodistribution results of rats. (author)

  4. Compound list: diazepam [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available diazepam DZP 00023 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/diaz...epam.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/diaz...epam.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/diaz...-tggates/LATEST/Rat/in_vivo/Liver/Repeat/diazepam.Rat.in_vivo.Liver.Repeat.zip ...

  5. (TH) diazepam binding to human granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bond, P.A.; Cundall, R.L.; Rolfe, B.

    1985-07-08

    (TH)-diazepam binds to sites on human granulocyte membranes, with little or no binding to platelets or lymphocytes. These (TH)-diazepam binding sites are of the peripheral type, being strongly inhibited by R05-4864 (Ki=6.23nM) but only weakly by clonazepam (Ki=14 M). Binding of (TH) diazepam at 0 is saturable, specific and stereoselective. Scatchard analysis indicates a single class of sites with Bmax of 109 +/- 17f moles per mg of protein and K/sub D/ of 3.07 +/- 0.53nM. Hill plots of saturation experiments gave straight lines with a mean Hill coefficient of 1.03 +/- 0.014. Binding is time dependent and reversible and it varies linearly with granulocyte protein concentration over the range 0.025-0.300 mg of protein. 11 references, 3 figures, 1 table.

  6. Capgras syndrome related to diazepam treatment.

    Science.gov (United States)

    Stewart, Jonathan T

    2004-01-01

    Capgras syndrome, the delusion that identical-appearing impostors have replaced familiar people, is an unusual phenomenon usually seen in schizophrenia or dementia. We recently cared for a 78 year old man who seemed to develop Capgras syndrome as an adverse reaction to diazepam. An iatrogenic cause should be considered in the differential diagnosis of any new delusion, including Capgras syndrome.

  7. Reversal of oxycodone and hydrocodone tolerance by diazepam.

    Science.gov (United States)

    Gonek, Maciej; Akbarali, Hamid I; Henderson, Graeme; Dewey, William L

    2017-11-01

    The Centers for Disease Control has declared opioid abuse to be an epidemic. Overdose deaths are largely assumed to be the result of excessive opioid consumption. In many of these cases, however, opioid abusers are often polydrug abusers. Benzodiazepines are one of the most commonly co-abused substances and pose a significant risk to opioid users. In 2016, the FDA required boxed warnings - the FDA's strongest warning - for prescription opioid analgesics and benzodiazepines about the serious risks associated with using these medications at the same time. The point of our studies was to evaluate the interactions between these two classes of drugs. We investigated whether diazepam adds to the depressant effects of opioids or do they alter the levels of tolerance to opioids. In the present study, we have found that the antinociceptive tolerance that developed to repeated administration of oxycodone was reversed by an acute dose of diazepam. Antinociceptive tolerance to hydrocodone was also reversed by acute injection of diazepam; however, a fourfold higher dose of diazepam was required when compared to reversal of oxycodone-induced tolerance. These doses of diazepam did not potentiate the acute antinociceptive effect of either opioid. The same dose of diazepam that reversed oxycodone antinociceptive tolerance also reversed oxycodone locomotor tolerance while having no potentiating effects. These studies show that diazepam does not potentiate the acute effect of prescription opioids but reverses the tolerance developed after chronic administration of the drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Diazepam and halazepam in anxiety: some prognostic indicators.

    Science.gov (United States)

    Rickels, K; Case, W G; Chung, H; Downing, R W; Vlahovich, J

    1978-01-01

    A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians.

  9. Feline hepatic biotransformation of diazepam: Differences between cats and dogs.

    Science.gov (United States)

    van Beusekom, Cyrina D; van den Heuvel, Jeroen J M W; Koenderink, Jan B; Russel, Frans G M; Schrickx, Johannes A

    2015-12-01

    In contrast to humans and dogs, diazepam has been reported to induce severe hepatic side effects in cats, particularly after repeated dosing. With the aim to elucidate the mechanisms underlying this apparent sensitivity of cats to drug-induced liver injury, in a series of in vitro experiments, the feline-specific biotransformation of diazepam was studied with liver microsomes obtained from cats and dogs and the possible inhibition of the bile salt export pump (Bsep) was measured in isolated membrane vesicles overexpressing feline and canine Bsep. In line with previous in vivo studies, the phase I metabolites nordiazepam, temazepam and oxazepam were measurable in microsomal incubations, although enzyme velocity of demethylases and hydroxylases differed significantly between cats and dogs. In cats, the main metabolite was temazepam, which also could be glucuronidated. In contrast to dogs, no other glucuronidated metabolites could be observed. In addition, in the membrane vesicles an inhibition of the transport of the Bsep substrate taurocholic acid could be observed in the presence of diazepam and its metabolites. It was concluded that both mechanisms, the slow biotransformation of diazepam as well the inhibition of the bile acid efflux that results in an accumulation of bile acids in the hepatocytes, seem to contribute to the liver injury observed in cats following repetitive treatment with diazepam. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Diazepam parenteral no tratamento de epilepsias graves Treatment of severe epilepsies with parenteral diazepam

    Directory of Open Access Journals (Sweden)

    José Geraldo Speciali

    1971-09-01

    Full Text Available As modificações dos quadros clínico e EEG foram estudadas em 9 pacientes com manifestações epilépticas rebeldes às medicações anticonvulsivantes habituais, quando submetidos à administração parenteral diária de diazepam (Valium e após sua interrupção. Houve diminuição do número e da duração das crises, superior a 75%, em três pacientes. Esses resultados são satisfatórios, considerando a gravidade dos quadros epilépticos e foram obtidos em pacientes com predomínio de alterações EEG lentas antes de iniciar o esquema terapêutico. Não se verificaram efeitos colaterais relevantes na época da administração parenteral. Em dois pacientes foi observado o aparecimento de crises tônicas coincidindo com o aumento de elementos EEG paroxísticos rápidos, localizados ou difusos.Changes of the clinical pictures and electroencephalographic patterns were studied in 9 patients suffering from epileptic seizures non responsive to common anticonvulsivants, when submitted to daily parenteral administration of diazepam (Valium and after its interruption. There was decrease of the number and duration of seizures, over to 75%, in 3 patients. These results can be considered as satisfatory, considering the intensity of the seizures. The best results were obtained in those patients which showed predominance of slow waves in the EEGs prior to the begin of the treatment. No side effects were observed during the treatment. Two patients developed tonic seizures coincident with the increasing of fast paroxistic EEG patterns, of localized or diffuse type.

  11. Phenobarbital versus diazepam for delirium tremens--a retrospective study

    DEFF Research Database (Denmark)

    Hjermø, Ida; Anderson, John Erik; Fink-Jensen, Anders

    2010-01-01

    Delirium tremens (DT) is a severe and potentially fatal condition that may occur during withdrawal from chronic alcohol intoxication. The purpose of the present study was to compare the effects and the rates of complications of phenobarbital and diazepam treatment in DT.......Delirium tremens (DT) is a severe and potentially fatal condition that may occur during withdrawal from chronic alcohol intoxication. The purpose of the present study was to compare the effects and the rates of complications of phenobarbital and diazepam treatment in DT....

  12. Feline hepatic biotransformation of diazepam: Differences between cats and dogs

    NARCIS (Netherlands)

    van Beusekom, Cyrina D; van den Heuvel, Jeroen J M W; Russel, Frans G M; Schrickx, Johannes A

    2015-01-01

    In contrast to humans and dogs, diazepam has been reported to induce severe hepatic side effects in cats, particularly after repeated dosing. With the aim to elucidate the mechanisms underlying this apparent sensitivity of cats to drug-induced liver injury, in a series of in vitro experiments, the

  13. Public judgments of information in a diazepam patient package insert.

    Science.gov (United States)

    Fisher, S; Mansbridge, B; Lankford, D A

    1982-06-01

    As part of a larger study of the effects of giving patients written take-home information with prescription medications, a "patient package insert" (PPI) for diazepam was prepared based on content determined by "experts." This report compares the experts' judgments of what information should be included with judgments obtained from the public. Information judged to be most important for inclusion in a PPI was identified by having subjects sort cards containing facts about diazepam. Subjects who had previously used diazepam were no different in their judgments than inexperienced subjects. In general, there was a high degree of concordance between public and expert judgments and also a remarkably strong consensus across very different demographic samples. In those few instances of disagreement, the public attached even greater importance to warnings and "bad news" about diazepam than to information providing reassurances, benign general education, and "good news." To what extent patients would effectively use this information--whether conveyed by PPIs or alternative educational routes--must await empirical evaluation.

  14. Tissue distribution of 14C-diazepam and its metabolites in rats

    International Nuclear Information System (INIS)

    Igari, Y.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.

    1982-01-01

    We have kinetically investigated the tissue distribution of 14 C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of 14 C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence

  15. Midazolam versus diazepam for combined esophogastroduodenoscopy and colonoscopy.

    Science.gov (United States)

    Brouillette, D E; Leventhal, R; Kumar, S; Berman, D; Kajani, M; Yoo, Y K; Carra, J; Tarter, R; Van Thiel, D H

    1989-08-01

    This study compares the effects of two different benzodiazepines used for conscious sedation during combined upper gastrointestinal endoscopy (EGD) and colonoscopy. Subjects were assessed for their degree of analgesia and amnesia for the procedure, prior experience with endoscopy, and willingness to undergo another similar procedure should such be necessary. The patients were randomized single blind to receive either midazolam or diazepam for their preprocedure sedation. The amount of preprocedure sedation utilized was determined by titration of the dose to achieve slurring of speech. Prior to receiving either agent, the subjects were shown a standard card containing pictures of 10 common objects, were asked to name and remember them, and were told they would be "quizzed" (at 30 min and 24 hr) after being sedated for their recollection as to the objects pictured on the card. Each subject filled out a questionnaire addressing their perceived discomfort during the endoscopic procedure and their memory of the procedure 24 hr after the procedure. Sixty-three percent of the midazolam-sedated subjects reported total amnesia for their colonoscopy vs 20% of diazepam-sedated patients (P less than 0.001). Fifty-three percent of midazolam-sedated patients reported total amnesia of their upper gastrointestinal endoscopy vs only 23% of diazepam-sedated subjects (P less than 0.05). The midazolam-sedated subjects reported experiencing less pain with both upper gastrointestinal endoscopy (P less than 0.05) and colonoscopy (P less than 0.001) than did the diazepam-sedated group. Most importantly, the midazolam group was more willing to undergo another similar endoscopic procedure should they be asked to do so by their physician (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    Science.gov (United States)

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  17. Quality control of 5mg diazepam suppositories manipulated in the city of Campos Goytacazes – RJ

    OpenAIRE

    Renata Aparecida Venturi Canzian; Fernanda Fraga Pessanha; Jean Carlos Brandão Storck

    2012-01-01

    Diazepam suppositories are widely used by children and elderly, and require close attention to quality control because it is a controlled prescription drug. The objective of the study was to analyze diazepam suppositories manipulated in Campos dos Goytacazes, RJ, to verify if they are within the required quality standards, and offer safety and efficiency to patients. We analyzed samples of 5mg diazepam suppositories acquired in five randomly selected pharmacies, identified as Pharmacy A, Phar...

  18. Effect of a polyethylene-lined administration set on the availability of diazepam injection.

    Science.gov (United States)

    Hancock, B G; Black, C D

    1985-02-01

    Delivery of diazepam through a polyethylene-lined i.v. administration set and through a polyvinyl chloride (PVC) set was compared. Diazepam was prepared in concentrations of 50 mg/500 mL and 100 mg/500 mL in 0.9% sodium chloride injection and 5% dextrose injection in glass containers. Diazepam concentrations were measured by high-performance liquid chromatography at 0 through 5 hours in samples collected simultaneously from the glass solution containers and from the distal ends of a PVC administration set and a polyethylene-lined (non-PVC) set. Flow rates of 50 and 100 mL/hr were tested. For the non-PVC sets, diazepam concentration in the infusate was not significantly different from concentration in the glass container at any sampling time. The overall percentage of diazepam recovered was 100.7 +/- 6.8%. For the PVC sets, diazepam concentration in the infusate was less than in the container at all sampling times, and the overall percentage of diazepam recovered was 65.4 +/- 13.3% (significantly different from delivery for the non-PVC sets). Delivery through the non-PVC sets was not affected by flow rate, type of solution, or concentration of diazepam. For infusion periods of up to five hours, delivery of diazepam through polyethylene-lined i.v. administration sets was superior to delivery through polyvinyl chloride sets.

  19. Central inhibition of initiation of swallowing by systemic administration of diazepam and baclofen in anaesthetized rats.

    Science.gov (United States)

    Tsujimura, Takanori; Sakai, Shogo; Suzuki, Taku; Ujihara, Izumi; Tsuji, Kojun; Magara, Jin; Canning, Brendan J; Inoue, Makoto

    2017-05-01

    Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. NEW & NOTEWORTHY Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. Copyright © 2017 the American Physiological Society.

  20. The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats.

    Science.gov (United States)

    Gai, N; Grimm, V E

    1982-01-01

    In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning: motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varying complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy was either 2.5, 5, of 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dose-dependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam- and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.

  1. Intermittent diazepam prophylaxis in febrile convulsions. Pros and cons.

    Science.gov (United States)

    Knudsen, F U

    1991-01-01

    Major cohort studies document that the long-term prognosis for most children with febrile convulsions (FC) is excellent. The 2 main treatment alternatives so far have been long-term prophylaxis with phenobarbital or valproate or no prophylaxis at all. Phenobarbital at times of fever is ineffective and obsolete. Consensus has emerged that long-term prophylaxis with antiepileptic drugs is rarely justified in FC considering the side effects and the favourable prognosis. No treatment at all does not appear quite satisfactory either, as FC have a high recurrence rate, disrupt family life and may have emotional consequences for the family. Moreover, all FC children face a risk, although admittedly low, of subsequent long-lasting potentially central nervous system (CNS)-damaging seizures. However, 2 further options exist: treatment with rapid-acting benzodiazepines solely at times of greatest risk, i.e., at high fever or at renewed seizures. Several clinical trials have confirmed that intermittent diazepam prophylaxis by way of a few doses of the drug per year provides effective seizure control and reduces the recurrence rate by one half or two thirds. The treatment is feasible and cheap, well tolerated by the child and well accepted by the parents. Compliance problems are common and only partly abatable. Trivial side effects are frequent. Transient respiratory apnoea does occur, but 15 years' experience substantiates that serious side effects are remarkably rare. Acute anticonvulsant treatment with rectal diazepam in solution given by the parents to stop ongoing seizures and to prevent immediate recurrences is an attractive alternative. It is feasible, is probably effective and minimizes the use of drugs, but compliance problems are common and protracted seizures are not always controlled. The subsequent management should include a risk profile approach considering a combination of risk factors for new FC rather than a single factor. By means of a risk index, based on

  2. The effect of the diazepam to the free radical under the brain radiation injury

    International Nuclear Information System (INIS)

    Huo Hongmei; Wang Chen; Zhang Zhilin

    2007-01-01

    Objective: To study the effect of the diazepam on free radical under in the brain radiation injury in the early stage. Methods: A model of whole brain radiation injury in wakefulness was established in the Sprague-Dawley rat. Diazepam was given intraperitoneally 30 minutes before radiation. The brain tissue homogenate was prepared respectively while the rats were executed 6 hours, 1 day, 1 week, 1 month after irradiation. The contents of the superoxide dismutase (SOD) and the malondialdehyde (MDA) in the tissue homogenate were measured by chemical colorimetry. Results: Diazepam could increase the vigor of SOD and reduce the MDA contents after irradiated. Conclusions: Diazepam has certain neuroprotection effect on radiation injury and decreasing the level of the free radicals. (authors)

  3. Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness.

    Science.gov (United States)

    Hirabayashi, Yu; Okumura, Akihisa; Kondo, Taiki; Magota, Miyuki; Kawabe, Shinji; Kando, Naoyuki; Yamaguchi, Hideaki; Natsume, Jun; Negoro, Tamiko; Watanabe, Kazuyoshi

    2009-06-01

    To assess the efficacy of diazepam suppositories at preventing febrile seizure recurrence during a single febrile illness to determine how to treat children with a febrile seizure on presentation at the hospital. We studied 203 children with febrile seizures from December 2004 through March 2006. On admission between December 2004 and May 2005, a diazepam suppository was administered to the patients. Patients seen between June 2005 and March 2006 were not treated with antiepileptic drugs on admission. We saw a significant difference in the rate of recurrence of febrile seizures between children treated with diazepam and those who were not. Recurrences were observed in 2 (2.1%) of 95 children treated with diazepam and in 16 (14.8%) of 108 untreated children. For the 108 untreated patients, the median age was 22.8 months in those with recurrences and 30.6 months in those without, confirming that a younger age was related to a recurrence. A diazepam suppository after a febrile seizure will reduce the incidence of recurrent febrile seizures during the same febrile illness. However, a diazepam suppository after a febrile seizure should be used after carefully considering the benefits and potential adverse effects.

  4. RP-HPLC Estimation of Imipramine Hydrochloride and Diazepam in Tablets.

    Science.gov (United States)

    Srikantha, D; Raju, R R

    2015-01-01

    A simple and rapid reversed phase-high performance liquid chromatographic method was developed for simultaneous determination of imipramine hydrochloride and diazepam in pharmaceutical formulations. The elution was done in isocratic mode utilizing a mobile phase consisting of methanol:water:0.1M sodium acetate (30:50:20 v/v/v) on Chromosil C18 column with a flow rate of 1.0 ml/min and with detection at 243 nm. The measured retention time was 3.33±0.02 min for imipramine hydrochloride and 4.64±0.02 min for diazepam. Linearity was measured in the range 25-150 μg/ml for imipramine hydrochloride (r(2)=0.999) and in the range 5-30 μg/ml for diazepam (r(2)=0.9994), respectively. The limits of detection and quantitation were 0.03 and 0.1 μg/ml for imipramine hydrochloride and 0.02 and 0.07 μg/ml for diazepam. Satisfactory validation was also obtained from recovery (100.95-101.52% for imipramine hydrochloride and 99.47-100.33% for diazepam) studies, intraday and interday precision (hydrochloride and diazepam in tablets.

  5. Detomidine-diazepam-ketamine anaesthesia in buffalo (Bubalus bubalis) calves.

    Science.gov (United States)

    Pawde, A M; Amarpal; Kinjavdekar, P; Aithal, H P; Pratap, K; Bisht, G S

    2000-04-01

    Eight buffalo calves (8-12 months, 70-100 kg) were randomly assigned to two groups of four animals each. Animals of group I were given detomidine (100 micrograms/kg), whereas animals of group II received a mixture of detomidine (100 micrograms/kg), diazepam (100 micrograms/kg) and ketamine (3 mg/kg) (DDK) intravenously. Various clinical parameters, such as weak time, down time, pedal and pinprick reflexes, muscle relaxation and extent of sedation, as well as heart and respiratory rates and electrocardiograms were measured before (time 0) and 15, 30, 45, 60, 75 and 90 min after treatment. In all the animals of group II (DDK), the pedal reflex was completely abolished (score: 3.00 +/- 0.00) within 5 min, the pinprick response was either very weak or it was completely abolished at this interval. Muscle relaxation and sedation were excellent within 5 min of DDK administration. The depth of sedation and analgesia was maximum from 5 to 15 min postinjection. Detomidine alone, however, failed to produce appropriate depression of the pedal and pinprick reflexes, sedation was mild and muscle relaxation was inadequate. Heart rate showed a significant (P detomidine. The results indicated that DDK combination is safe and suitable for 15 min of anaesthesia with excellent muscle relaxation and has only limited cardiorespiratory effects in buffaloes.

  6. Chromosomal localization of the human diazepam binding inhibitor gene

    International Nuclear Information System (INIS)

    DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

    1988-01-01

    The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes

  7. Short-term and long-term effects of diazepam on the memory for discrimination and generalization of scopolamine.

    Science.gov (United States)

    Casasola-Castro, C; Weissmann-Sánchez, L; Calixto-González, E; Aguayo-Del Castillo, A; Velázquez-Martínez, D N

    2017-10-01

    Benzodiazepines are among the most widely prescribed and misused psychopharmaceutical drugs. Although they are well-tolerated, they are also capable of producing amnestic effects similar to those observed after pharmacological or organic cholinergic dysfunction. To date, the effect of benzodiazepine diazepam on the memory for discrimination of anticholinergic drugs has not been reported. The aim of the present study was to analyze the immediate and long-term effects of diazepam on a drug discrimination task with scopolamine. Male Wistar rats were trained to discriminate between scopolamine and saline administration using a two-lever discrimination task. Once discrimination was acquired, the subjects were divided into three independent groups, (1) control, (2) diazepam, and (3) diazepam chronic administration (10 days). Subsequently, generalization curves for scopolamine were obtained. Additionally, the diazepam and control groups were revaluated after 90 days without having been given any other treatment. The results showed that diazepam produced a significant reduction in the generalization gradient for scopolamine, indicating an impairment of discrimination. The negative effect of diazepam persisted even 90 days after drug had been administered. Meanwhile, the previous administration of diazepam for 10 days totally abated the generalization curve and the general performance of the subjects. The results suggest that diazepam affects memory for the stimulus discrimination of anticholinergic drugs and does so persistently, which could be an important consideration during the treatment of amnesic patients with benzodiazepines.

  8. Myocardial Function of Hyperthyroid Rats in Presence of Diazepam in Langendorff Setup

    Directory of Open Access Journals (Sweden)

    Atefeh Asadmobini

    2015-06-01

    Full Text Available Background: Modulation of Ischemia-Reperfusion (I/R injury is highly important in medicine, especially in hyperthyroidism condition. The effect of diazepam as a benzodiazepine on cardiac I/R injury is also clinically important. The chronic effect of diazepam in this case has been reported previously. Objectives: This study aimed to investigate the effect of acute diazepam perfusion on isolated heart of hyperthyroid rats during I/R. Materials and Methods: Male rats (n = 32, weighing 250 - 300 gr were randomly divided into 4 groups: control, hyperthyroid, control diazepam perfused, and hyperthyroid diazepam perfused. Isolated hearts were perfused through Langendorff method. Four sets of data were collected at baseline (20 minutes, diazepam perfusion (10 minutes, 100 µmol/L, ischemia (40 minutes, and reperfusion (45 minutes periods. Cardiac parameters, including Left Ventricular Developed pressure (LVDP; mmHg and Rate Pressure Product (RPP; mmHg × beats/min were measured, as well. Lactate dehydrogenase (LDH; mU/mL was also assessed for evaluation of I/R injury. The data were analyzed using ANOVA and Student t-test and P < 0.05 was considered as statistically significant. Results: RPP significantly declined in the hyperthyroid group after diazepam perfusion compared to the baseline (24046 ± 1381 versus 18269 ± 711, P = 0.012, 95% CI: 1724 - 9828. Besides, RPP and LVDP significantly increased in the hyperthyroid diazepam perfused group compared to the hyperthyroid group at the end of the reperfusion period (12469 ± 1422 versus 4007 ± 258, P < 0.001, CI: 5066 - 11856 and 47 ± 2.8 versus 23 ± 2.8, P < 0.001, CI: 11-35, respectively. These findings were confirmed by LDH levels (19.08 ± 1.06 versus 41.07 ± 8.14, P = 0.002, CI: -34.4 - -9.4-35. Conclusions: The results showed that acute diazepam perfusion to isolated hyperthyroid rats’ hearts could significantly improve cardiac function following ischemia and protect the heart against I

  9. Effects of diazepam on Mycobacterium bovis-induced infection in hamsters

    Directory of Open Access Journals (Sweden)

    Righi D.A.

    1999-01-01

    Full Text Available The in utero exposure of hamsters to low doses of diazepam results in impaired host defense against Mycobacterium bovis during adulthood. Delayed developmental immunotoxicity, however, represents a specific situation that might not be general. The present experiment was undertaken to investigate the effects of diazepam on hamster resistance to M. bovis using adult animals. The effects of diazepam treatment on serum cortisol levels were also studied. Adult hamsters (N = 10 for each group were treated with diazepam (E1 = 1.0, E2 = 2.0 or E3 = 3.0 mg kg-1 day-1 subcutaneously or with control solution (C for 30 days. Seven days after the beginning of the treatment, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with the higher (2.0 and 3.0 mg kg-1 day-1 doses of diazepam exhibited: 1 increased granuloma areas in the liver (C = 1.81 ± 1.39, E2 = 10.29 ± 4.64 and E3 = 15.80 ± 4.82 and lung (C = 0.54 ± 0.55, E2 = 6.28 ± 3.85 and E3 = 6.31 ± 3.56 and 2 increased scores of M. bovis colony-forming units isolated from liver (C = 2.0, E2 = 3.0 and E3 = 3.5, lung (C = 1.0, E2 = 3.0 and E3 = 3.5 and spleen (C = 1.0, E2 = 2.5 and E3 = 4.0. These effects were dose dependent, and were not detected or were less severe in animals treated with the lowest (1.0 mg/kg dose of diazepam as well as in those of the control group. Furthermore, diazepam treatment (3.0 mg kg-1 day-1 for 30 days increased (E3 = 71.32 ± 2.99; N = 10 the serum levels of cortisol compared to control hamsters (C = 22.61 ± 2.75; N = 10. The present data, that demonstrate an impaired defense against M. bovis in adult hamsters treated with diazepam, were tentatively explained on the basis of a direct and/or indirect action of diazepam on the cytokine network. The effects may be related to stimulation of peripheral benzodiazepine receptor binding sites (PBR by macrophages and/or lymphocytes, or they may be mediated by PBR stimulation of the adrenals.

  10. Hyoscine versus diazepam for the management of true vertigo in the emergency department

    Directory of Open Access Journals (Sweden)

    Hamid Kariman

    2017-06-01

    Full Text Available The present study was a double-blind clinical trial to compare the efficiency of hysocine and diazepam in vertigo treatment. Eligible patients (n=69 were randomly divided into 2 groups of 5 mg hyoscine and 10 mg diazepam. Severity of vertigo was measured in supine and sitting position, and while turning the head. Vertigo severity was assessed before, and 1 and 2 hours after administration of the drug. Treatment success rate of diazepam in relieving vertigo in different positions varied between 88.9 and 100%, while this rate was 31.2–73.5% in hyoscine treatment group (p<0.01. Prescription of diazepam led to complete relief of vertigo in 40–63% of the patients, while this rate was only 2.6–12.5% in hyoscine treatment group (p<0.001. It is likely that diazepam is a better option than hyoscine for management of true vertigo in patients presenting to the emergency department.

  11. The effect of baclofen and diazepam on motor skill acquisition in healthy subjects

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Maria; Lundbye-Jensen, Jesper; Petersen, Tue Hvass

    2011-01-01

    investigated the influence of baclofen and diazepam on acquisition of a visuomotor skill. The study was designed as a semi-randomized, double-blinded, placebo-controlled, crossover study in 16 healthy human subjects. The motor skill task required the subjects to match a given force trajectory by increasing...... that diazepam and baclofen interfere with the acquisition of a motor skill by disrupting some of the neuroplastic changes that are involved in improved motor performance. This suggests that antispastic treatment should be used with caution in subjects receiving concomitant physiotherapy.......Antispastic medication is often used in the clinic together with physiotherapy. However, some of the antispastic drugs, e.g., baclofen and diazepam, may influence the plastic mechanisms that are necessary for motor learning and hence efficient physiotherapy. In the present study, we consequently...

  12. Vestibulo-ocular reflexes in rabbits: reduction by intravenous injection of diazepam.

    Science.gov (United States)

    Barmack, N H; Pettorossi, V E

    1980-11-01

    We have studied the influence of intravenously administered diazepam on the horizontal (HVOR) and vertical (VVOR) vestibulo-ocular reflexes of the rabbit. The HVOR and VVOR were evoked by sinusoidal oscillation of rabbits on a rate table (0.01 to 0.8 Hz, +/- 10 degrees), and eye movements were measured with an infrared light-projection technique. The gains of the HVOR and VVOR (evoked eye velocity/head velocity) were reduced by diazepam injections of 5 microgram/kg. The dose required to produce a 50% reduction in HVOR gain was 500 microgram/kg. The time required to reduce the HVOR gain to 50% of its maximal reduction at dose of 400 microgram/kg (0.4 Hz +/- 10 degrees) was 60 s. These data suggest that diazepam might be effective as an anti-motion-sickness agent.

  13. Lab on paper chip integrated with Si@GNRs for electroanalysis of diazepam

    International Nuclear Information System (INIS)

    Narang, Jagriti; Singhal, Chaitali; Mathur, Ashish; Khanuja, Manika; Varshney, Ankur; Garg, Kartikey; Dahiya, Tulika; Pundir, C.S.

    2017-01-01

    We describe herein the fabrication of an electrochemical microfluidic paper based device (EμPAD) for the detection of diazepam, a sedative, anxiety-relieving and muscle-relaxing drug. To achieve it, silica coated gold nanorods (Si@GNRs) were synthesized and drop casted on an electrochemical microfluidic paper based device (EμPAD) for the detection of diazepam. The synthesized composites were characterized by recording its images in scanning electron microscope (SEM) and transmission electron microscope (TEM). The experimental results confirmed that Si@GNRs had good electrocatalytic activity towards diazepam. The modified paper based electrode showed a stable electrochemical response for diazepam in the concentration range of 3.5 nM to 3.5 mM. EμPAD offers many advantageous features such as facile approach, economical and have potential for commercialization. Si@GNRs modified EμPAD was also employed for determination of diazepam in spiked human urine samples. Reported facile lab paper approach integrated with Si@GNRs could be well applied for the determination of serum metabolites. - Highlights: • EμPAD offers many advantageous features such as facile approach, economic and have potential for commercialization. • Extensive development can be made for industrial translation of this fabricated device. • Si@GNR modified EμPAD showed wide linear range of 3.5 nM to 3.5 mM. • The detection limit was as low as 1.5 x 10 −9 M for diazepam detection. • The developed sensor was tested in real time samples like injection, tablets and found good correlation.

  14. Influence of hydrogen peroxide in drinking water on diazepam pharmacokinetics in chicks

    Directory of Open Access Journals (Sweden)

    Yaareb J. Mousa

    Full Text Available Aim: Stressful conditions affect drug pharmacokinetics and pharmacodynamics. This study examines the effect of hydrogen peroxide (H2O2 in drinking water on the pharmacokinetics of diazepam in a chick model of oxidative stress. Materials and Methods: Day old chicks were either provided with plane tap water (control group or H2O2 in tap water as 0.5% v/v drinking solution for two weeks in order to produce oxidative stress. On treatment days 7–14, the chicks were treated with a sedative dose of diazepam at 10 mg/kg, intramuscularly. Blood samples were obtained from chicks (5/each sampling time at times of between 0.17 to 4 h. The concentrations of diazepam in the plasma were determined by an HPLC method with UV-detector. Pharmacokinetic parameters of diazepam were calculated from the mean drug concentrations in the plasma by a non-compartmental analysis using a Windows-based computer program. Results: Injection of diazepam resulted in the appearance of the drug in the plasma of control and H2O2 -treated chicks at mean concentrations ranging between 0.11 to 0.444 and 0.131 to 0.535 μg/ml, respectively when measured between 0.17 to 4 h after administration. Diazepam concentrations of the H O -treated chicks were significantly higher than those of the control group at the sampling times 0.5, 0.75, 1 and 4 h. The highest concentration of diazepam in the plasma of both the control and H2O2 treated chicks occurred one h after the injection. The elimination half-life, mean residence time, maximum plasma concentration, area under the moment curve and area under plasma concentration-time curve in the H2O2 -treated chicks were higher than those of the control group by 35, 28, 23, 91 and 49%, respectively. Correspondingly, the steady state volume of distribution, elimination rate constant and total body clearance in the H2O2 -treated chicks decreased from those of the respective control values by 15, 24 and 33%. Conclusion: The data suggest that oral

  15. Behavioral pharmacology and verbal behavior: Diazepam effects on verbal self-reports

    OpenAIRE

    Critchfield, Thomas S.

    1993-01-01

    Diazepam (10 mg) was administered to two men performing a delayed matching-to-sample task in which the number of elements in a compound sample stimulus (one of which appeared among 4 comparison stimuli) was manipulated from 1 to 3. After each trial, subjects pressed either a “Yes” or “No” button in response to a computer-presented query about whether the last choice met a point contingency requiring selection of the matching comparison stimulus within a time limit. Diazepam simultaneously pro...

  16. A new nasal drug delivery system for Diazepam using natural Mucoadhesive Polysaccharide obtained from tamarind seeds

    International Nuclear Information System (INIS)

    Datta, R.; Bandyopadhyaya, Amal K.

    2006-01-01

    A new nasal drug delivery system of diazepam has been developed with a natural mucoadhesive agent from Tamarindus indica L. The mucoadhesive strength, viscosity and gelling property of this natural mucoadhesive agent was found to be higher in comparison to synthetic polymers, hydroxyl propyl methyl cellulose (HPMC) and carbopol 934 which are conventionally used for similar purpose. In vitro drug release characteristic through franz-diffusion cell using excised bovine nasal membrane was also found to be better in comparison to the above synthetic polymers. This patient friendly, needle free dosage form may replace the diazepam injections in future. (author)

  17. Determination of diazepam and its metabolites in serum by the use of liquid chromatography: Mass spectrometry method

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2007-01-01

    Full Text Available Background/Aim. Diazepam is a benzodiazepine anxyolitic. Metabolism of diazepam takes place in liver which generates pharmacologically active metabolites N-desmethyldiazepam, temazepam and oxazepam. The aim of this study was to develop and validate the method of liquid chromatographymass spectrometry (LC-MS for separation and determination of diazepam and its active metabolites in the serum of rats samples after i.p. application of diazepam in a dose of 10 mg/kg. Methods. The serum samples taken from Wistar rats, were used in LC-MS analysis after the application of 10 mg/kg of diazepam i.p. Results. After alkaline extraction from the serum samples with diethylether and separation on a C18 reversed-phase column by using mobile phase methanolglacial acetic acid-water (50:1:49 v/v, diazepam and its metabolites were quantified. Determination was performed in a selective ion monitoring (SIM mode, thereby the other exogenous and endogenous compounds did not interfere with this assay. Diazepam, N-desmethyldiazepam, oxazepam and temazepam were eluted in 14 minutes. The standard curve was linear in the range from 10-2 000 ng/ml. The limits of detection for diazepam, N-desmethyldiazepam, oxazepam and temazepam were 4.37, 3.13, 4.38 and 7.31 ng/ml, respectively. The limits of quantitation for diazepam, Ndesmethyldiazepam, oxazepam and temazepam were 14.58, 10.41, 14.59 and 24.36 ng/ml, respectively. Conclusion. The described LC-MS is a simple, sensitive, specific and accurate method and could be used for routine identification and quantification of small concentrations of diazepam and its metabolites in biological fluids.

  18. The effects of diazepam and zolpidem on cocaine- and amphetamine-induced place preference.

    Science.gov (United States)

    Meririnne, E; Kankaanpää, A; Lillsunde, P; Seppälä, T

    1999-01-01

    Drugs such as benzodiazepines, which enhance the effects of inhibitory neurotransmitter gamma-amino butyric acid (GABA), are known to modulate the mesocorticolimbic dopaminergic system, which is considered to mediate the rewarding effects of psychostimulants. The effects of diazepam, a benzodiazepine that binds unspecifically to omega 1- (omega1-) and omega2-receptors, and zolpidem, a nonbenzodiazepine drug that binds preferentially to omega1-receptors, on cocaine- and amphetamine-induced place preference were evaluated in Wistar rats. In tests using the counterbalanced method, neither diazepam (0.2, 1, and 5 mg/kg) nor zolpidem (2.5, 5, and 10 mg/kg) alone induced place preference or place aversion. Diazepam pretreatment prevented both cocaine- and amphetamine-induced (15 and 9 mg/kg, respectively) place preference; however, at doses that were earlier shown to cause sedation and amnesia, zolpidem failed to prevent either cocaine- or amphetamine-induced place preference. These results suggest that diazepam interferes with the rewarding properties of the psychostimulants, whereas zolpidem is less effective in this respect, possibly due to differential distribution of omega1- and omega2-receptors in the brain.

  19. Ernstige intoxicatie met hydroxychloroquine, met hemodynamische instabiliteit : casuistische ondersteuning voor behandeling met diazepam

    NARCIS (Netherlands)

    Olgers, T J; Tulleken, J E; Monteban-Kooistra, W E; Ligtenberg, J J M; Meertens, J H; Zijlstra, J.G.

    2008-01-01

    A 37-year-old woman was admitted to the emergency room because of an autointoxication with hydroxychloroquine, leading to haemodynamic instability. Treatment consisted of the rapid administration of intravenous diazepam, after which the hypotension recovered rapidly even though no vasoactive

  20. 75 FR 51080 - Determination That DIASTAT (Diazepam Rectal Gel), 5 Milligrams/Milliliter, 10 Milligrams/2...

    Science.gov (United States)

    2010-08-18

    ... Evaluations,'' which is generally known as the ``Orange Book.'' Under FDA regulations, drugs are removed from... (diazepam rectal gel) is an anticonvulsant agent indicated for use in the management of selected, refractory... strengths of the product were moved to the ``Discontinued Drug Product List'' section of the Orange Book. We...

  1. The role of albumin conformation in the binding of diazepam to human serum albumin

    NARCIS (Netherlands)

    Wilting, J.; Hart, B.J. 't; Gier, J.J. de

    2006-01-01

    The effect of hydrogen, chloride and calcium ions on the binding of diazepare to human serum albumin has been studied by circular dichroism and equilibrium dialysis. In all cases the molar ellipticity of the diazepam-albumin complex increases with pH over the pH range 5 to 9. Under these

  2. Diazepam prophylaxis of contrast media-induced seizures during computed tomography of patients with brain metastases

    International Nuclear Information System (INIS)

    Pagani, J.J.; Hayman, L.A.; Bigelow, R.H.; Libshitz, H.I.; Lepke, R.A.; Wallace, S.

    1983-01-01

    The effect of 5 mg of intravenous diazepam (Valium) on contrast media-associated seizer incidence was studied in a randomized controlled trial involving 284 patients with known or suspected brain metastases undergoing cerebral computed tomography. Of these patients, 188 were found to have brain metastases, and it is estimated that for this subgroup prophylactic diazepam reduces the risk of contrast-assocated seizure by a factor of 0.26. Seizures occurred in three of 96 patients with metastases on diazepam and in 14 of 92 patients with metastases but without diazepam. Factors related to increased risk of contrast media-associated seizures are: (1) prior seizure history due to brain metatases and/or prior contrast, (2) progressive cerebral metastases, and (3) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of these seizures are: (1) contrast media dosage, chemical composition, or osmolarity, (2) computed tomographic appearance of metastases, and (3) type of primary malignancy. Concomitant therapeutic levels of diphenylhydantoin (Dilantin) do not protect completely against contrast media-associated seizures. Pathophysiology of contrast media-associated seizures is discussed in view of the risk factors determined by this study

  3. Anaesthetic induction and recovery characteristics of a diazepam-ketamine combination compared with propofol in dogs

    Directory of Open Access Journals (Sweden)

    Jacques P. Ferreira

    2015-06-01

    Full Text Available Induction of anaesthesia occasionally has been associated with undesirable behaviour in dogs. High quality of induction of anaesthesia with propofol has been well described while in contrast variable induction and recovery quality has been associated with diazepam-ketamine. In this study, anaesthetic induction and recovery characteristics of diazepam-ketamine combination with propofol alone were compared in dogs undergoing elective orchidectomy. Thirty-six healthy adult male dogs were used. After habitus scoring (simple descriptive scale [SDS], the dogs were sedated with morphine and acepromazine. Forty minutes later a premedication score (SDS was allocated and general anaesthesia was induced using a combination of diazepam-ketamine (Group D/K or propofol (Group P and maintained with isoflurane. Scores for the quality of induction, intubation and degree of myoclonus were allocated (SDS. Orchidectomy was performed after which recovery from anaesthesia was scored (SDS and times to extubation and standing were recorded. Data were analysed using descriptive statistics and Kappa Reliability and Kendall Tau B tests. Both groups were associated with acceptable quality of induction and recovery from anaesthesia. Group P, however, was associated with a poorer quality of induction (p = 0.014, prolonged induction period (p = 0.0018 and more pronounced myoclonus (p = 0.003, but had better quality of recovery (p = 0.000002 and shorter recovery times (p = 0.035 compared with Group D/K. Diazepam-ketamine and propofol are associated with acceptable induction and recovery from anaesthesia. Propofol had inferior anaesthetic induction characteristics, but superior and quicker recovery from anaesthesia compared with diazepam-ketamine.

  4. Diffusion of [2-14C]diazepam across hairless mouse skin and human skin

    International Nuclear Information System (INIS)

    Koch, R.L.; Palicharla, P.; Groves, M.J.

    1987-01-01

    The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber

  5. Two compartment model of diazepam biotransformation in an organotypical culture of primary human hepatocytes

    International Nuclear Information System (INIS)

    Acikgoez, Ali; Karim, Najibulla; Giri, Shibashish; Schmidt-Heck, Wolfgang; Bader, Augustinus

    2009-01-01

    Drug biotransformation is one of the most important parameters of preclinical screening tests for the registration of new drug candidates. Conventional existing tests rely on nonhuman models which deliver an incomplete metabolic profile of drugs due to the lack of proper CYP450 expression as seen in human liver in vivo. In order to overcome this limitation, we used an organotypical model of human primary hepatocytes for the biotransformation of the drug diazepam with special reference to metabolites in both the cell matrix phase and supernatant and its interaction of three inducers (phenobarbital, dexamethasone, aroclor 1254) in different time responses (1, 2, 4, 8, 24 h). Phenobarbital showed the strongest inducing effect in generating desmethyldiazepam and induced up to a 150 fold increase in oxazepam-content which correlates with the increased availability of the precursor metabolites (temazepam and desmethyldiazepam). Aroclor 1254 and dexamethasone had the strongest inducing effect on temazepam and the second strongest on oxazepam. The strong and overlapping inductive role of phenobarbital strengthens the participation of CYP2B6 and CYP3A in diazepam N-demethylation and CYP3A in temazepam formation. Aroclor 1254 preferentially generated temazepam due to the interaction with CYP3A and potentially CYP2C19. In parallel we represented these data in the form of a mathematical model with two compartments explaining the dynamics of diazepam metabolism with the effect of these other inducers in human primary hepatocytes. The model consists of ten differential equations, with one for each concentration c i,j (i = diazepam, temazepam, desmethyldiazepam, oxazepam, other metabolites) and one for each compartment (j = cell matrix phase, supernatant), respectively. The parameters p k (k = 1, 2, 3, 4, 13) are rate constants describing the biotransformation of diazepam and its metabolites and the other parameters (k = 5, 6, 7, 8, 9, 10, 11, 12, 14, 15) explain the

  6. Modification by diazepam or thioridazine of the psychomotor skills related to driving: a subacute trial in neurotic out-patients.

    Science.gov (United States)

    Saario, I; Linnoila, M; Mattila, M J

    1976-01-01

    Forty-five out-patients with clinically manifested anxiety were tested in order to study the effects of 2 weeks' treatment with placebo, diazepam (5-10 mg three times daily) or thioridazine (25-50 mg three times daily) on their psychomotor skills related to driving. When compared with placebo, diazepam increased the number of mistakes in reaction and co-ordination tests and also decreased ability to discriminate the fusion of flickering light. When compared to other groups, reactive and co-ordinative skills were more impaired in patients treated with thioridazine which also impaired divided attention. Aubjectively thioridazine was not experienced as effective an anxiolytic as diazepam. PMID:973981

  7. Intermittent diazepam and continuous phenobarbital to treat recurrence of febrile seizures: a systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Masuko Alice Hatsue

    2003-01-01

    Full Text Available Convulsions triggered by fever are the most common type of seizures in childhood, and 20% to 30% of them have recurrence. The prophylactic treatment is still controversial, so we performed a systematic review to find out the effectiveness of continuous phenobarbital and intermittent diazepam compared to placebo for febrile seizure recurrence. METHOD: Only randomized, double-blind, placebo-controlled trials were analyzed. The recurrence of febrile seizure was assessed for each drug. RESULTS: Ten eligible clinical trials were included. Febrile seizure recurrence was smaller in children treated with diazepam or phenobarbital than in placebo group. Prophylaxis with either phenobarbital or diazepam reduces recurrences of febrile seizures. The studies were clinical, methodological, and statistically heterogeneous. CONCLUSION: The effectiveness of phenobarbital and diazepam could not be demonstrated because clinical trials were heterogeneous, and the recommendation for treatment recurrence should rely upon the experience of the assistant physician yet.

  8. Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine.

    Science.gov (United States)

    Bédard, Anne-Catherine; Longstreet, Ashley R; Britton, Joshua; Wang, Yuran; Moriguchi, Hideki; Hicklin, Robert W; Green, William H; Jamison, Timothy F

    2017-12-01

    Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A comparative study of clonidine versus a combination of diazepam and atropine for premedication in orthopaedic patients.

    Directory of Open Access Journals (Sweden)

    Chaurasia S

    1999-07-01

    Full Text Available Sixty patients in the age group of 18-60 years of A.S.A. Grade I/II risk, scheduled for elective orthopaedic surgeries under general anaesthesia were studied for pre-medication with either oral clonidine or with combination of effects of diazepam & atropine. Patients in Group A (clonidine group received tablet clonidine 100 mcg (1 tablet if less than 50 kg in weight and 200 mcg if weighing more than 50 kg two hours before surgery. Patients in Group B (Diazepam-atropine group received one tablet of Diazepam (10 mg orally two hours before surgery and injection atropine-sulphate 0.01 mg/kg half an hour preoperatively by intramuscular route. In our study, the sedative and anti-sialogogue effects of clonidine were comparable to those of diazepam-atropine combination, which are commonly used premedicants. The anti-anxiety effect of clonidine was found to be better than that of diazepam-atropine combination. Clonidine also proved to be a better agent for the attenuation of pressor response to laryngoscopy and intubation. Thus, oral clonidine is a better premedicant compared to atropine-diazepam combination. Also, it is a more acceptable agent because of its oral route of administration.

  10. The effects of diazepam on the development of learned helplessness and depression

    OpenAIRE

    2015-01-01

    M.A. (Clinical Psychology) This study was undertaken in an attempt to validate the hypothesis that anxious subjects who ingested diazepam (Valium) and were subjected to a helplessness inducing situation,would become more depressed and more hopeless than people who were subjected to the same situation and obtained anxiety relief by means of a response-contingent behaviour - a muscle relaxation exercise. Twenty-nine male and female students were selected from the undergraduate and post-gradu...

  11. Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

    OpenAIRE

    Mattila, M J; Koski, J; Strömberg, C

    1987-01-01

    Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h af...

  12. A 5-year follow-up study of users of benzodiazepine: starting with diazepam versus oxazepam.

    Science.gov (United States)

    Tvete, Ingunn Fride; Bjørner, Trine; Skomedal, Tor

    2016-04-01

    Drug dependency may develop during long-term benzodiazepine use, indicated, for example, by dose escalation. The first benzodiazepine chosen may affect the risk of dose escalation. To detect possible differences in benzodiazepine use between new users of diazepam and oxazepam over time. This 5-year prescription database study included 19 747 new benzodiazepine users, inhabitants of Norway, aged 30-60 years, with first redemption for diazepam or oxazepam. Individuals starting on diazepam versus oxazepam were analysed by logistic regression with sex, age, other drug redemptions, prescriber's specialty, household income, education level, type of work, and vocational rehabilitation support as background variables. Time to reach a daily average intake of ≥1 defined daily doses (DDD) over a 3-month period was analysed using a Cox proportional hazard regression model. New users of oxazepam had a higher risk for dose escalation compared with new users of diazepam. This was true even when accounting for differences in sociodemographic status and previous drug use (hazard ratio [HR] 1.33, 95% confidence interval = 1.17 to 1.51). Most doctors prescribed, according to recommendations, oxazepam to individuals they may have regarded as prone to and at risk of dependency. However, these individuals were at higher risk for dose escalation even when accounting for differences in sociodemographic status and previous drug use. Differences between the two user groups could be explained by different preferences for starting drug, DDD for oxazepam being possibly too low, and some unaccounted differences in illness. © British Journal of General Practice 2016.

  13. Analysis of specific 3H-diazepam binding in the brain of emotionally difference mice

    International Nuclear Information System (INIS)

    Blednov, Yu.A.; Gordei, M.L.; Seredenin, S.B.

    1987-01-01

    A study of the behavior of inbred animals under conditions of emotional stress, of the biochemical parameters of the stress reaction, and of the effects of benzodiazepine tranquilizers, conducted in the authors' laboratory, showed that the character of the response to stress and the manifestation of the action of benzodiazepine depend on hereditary factors. The aim of this investigation was to study reception of tritium-labelled diazepam by brain cell membranes of C57BL/6 and BALB/c mice

  14. Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

    Science.gov (United States)

    Mattila, M J; Koski, J; Strömberg, C

    1987-02-01

    Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.

  15. Scope of harmonisation of pharmacopoeial liquid chromatography (LC) methods for diazepam and its related substances

    International Nuclear Information System (INIS)

    Shar, G.Q.; Jatoi, W.B.

    2015-01-01

    Drug analysis is an imperative activity to check the quality of a drug compound. Pharmacopoeial monographs provide important information about the quality of a drug substance. The expected quality of a medicine during period of use is also explained in such monographs. Analytical tools such as spectroscopic and chromatographic methods have been developed for such investigations. We have analysed the purity of a well known anxiolytic drug; diazepam, by using liquid chromatographic (LC) technique. It was noticed that with Zorbax Eclipse XDB - C8 (4.6 x 150 mm, 5 mu m) column and recommended mobile phase comprising acetonitrile - methanol -potassium dihydrogen phosphate (22+34+44 v/v), the desired results obtained were not according the chromatograms provided by European Pharmacopeia (EP), but by using another column (ACE- 5 - C8) (4.6 x 150 mm, 5 ?m), an extra peak of diazepam degradant was obtained, which showed that by using appropriate mobile phase containing CH3CN- CH/sub 3/OH- KH/sub 2/PO/sub 4/ (20+32+48 v/v), the better results can be achieved. The mean retention time for diazepam analysis was 2.9 minutes. (author)

  16. Rapid Relief of Catatonia in Mood Disorder by Lorazepam and Diazepam

    Directory of Open Access Journals (Sweden)

    Yu-Chi Huang

    2013-02-01

    Full Text Available Background: Catatonia has risks of severe morbidity and mortality and needs early treatment. In this study, we investigated more patients to discuss the efficacy of this treatment in patients with major depressive disorder (MDD or bipolar I disorder (BPI. Methods: During a period of 9 years, we identified 12 catatonic patients with mood disorder, with MDD (n = 10 and BPI (n = 2 in the emergency department, inpatient and outpatient units of a general hospital. The patients received intramuscular injection (IMI of 2 mg lorazepam once or twice during the first 2 h. If intramuscular lorazepam failed, intravenous dripping (IVD of 10 mg diazepam in 500 mL normal saline every 8 h for 1 day was prescribed. Results: Eight patients had full remission of catatonia after receiving one dose of 2 mg lorazepam IMI. Two patients needed two doses of 2 mg lorazepam IMI. Two patients with BPI recovered from catatonia using one dose of 10 mg diazepam IVD over 8 h after they failed to respond to two doses of 2 mg lorazepam IMI. The response rate to lorazepam IMI was 83.3%. All catatonic features remitted in 24 h with 100% response rate. Conclusions: The lorazepam-diazepam treatment strategy is a safe and effective method to relieve catatonia in mood disorder within 1 day. Psychiatrist consultation is helpful for final diagnosis and rapid treatment of catatonia.

  17. Quality control of 5mg diazepam suppositories manipulated in the city of Campos Goytacazes – RJ

    Directory of Open Access Journals (Sweden)

    Renata Aparecida Venturi Canzian

    2012-10-01

    Full Text Available Diazepam suppositories are widely used by children and elderly, and require close attention to quality control because it is a controlled prescription drug. The objective of the study was to analyze diazepam suppositories manipulated in Campos dos Goytacazes, RJ, to verify if they are within the required quality standards, and offer safety and efficiency to patients. We analyzed samples of 5mg diazepam suppositories acquired in five randomly selected pharmacies, identified as Pharmacy A, Pharmacy B, Pharmacy C, Pharmacy D, and Pharmacy E. We ran tests on average weight, organoleptic control, hardness, melting point, and dissolution. Data was analyzed and compared with the requirements of the Brazilian Pharmacopoeia. This analysis was made over a table in Excel. We conclude that only C Pharmacy was approved in all tests, and this is the only laboratory that has analyzed the quality of the product warranty. Laboratories A, B, D and E have been approved in some tests, and failed one or more tests. To ensure quality control, suppositories needed to pass in all tests, which was not the case of these labs. Therefore, we recommended the following procedures to the investigated laboratories: changes in packaging, greater precision in handling, quality control prior to dispensing the product, and efficient pharmaceutical care service.

  18. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    Science.gov (United States)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  19. Comparison of Trazodone, Diazepame and Dibenzepine Influences on Rat Brain Beta-Endorphins Content

    Directory of Open Access Journals (Sweden)

    Radivoj Jadrić

    2007-08-01

    Full Text Available The aim of our study was to establish the extent of influence of different psychotropic drugs to brain β-endorphins in experimental animals. The study was performed on albino Wistar rats (weight 250 g, treated with different psychoactive drugs. RIA technique was employed for quantification of brain β-endorphins. Brain β-endorphins were higher in experiment group treated with trazodone (929 pg/g ± 44,43; X±SD, and dibenzepine (906,63 pg/g ± 74,06, yet with lower brain content in rats treated with diazepame (841,55 pg/g ± 68,47, compared to brain β-endorphins content of control group treated with saline solution (0,95% NaCl (873,5 pg/g ± 44,89. Significant differences were obtained comparing brain β-endorphins of trazodone vs. diaze-pame treated animals, with diazepame group having lower values (p<0,02. This study showed differences in changes of rat brain β-endorphins contents when different psy-choactive drugs are used. Therefore, we consider that β-endorphins could be used for evaluation of effects of psychoactive drugs, as a useful parameter in therapy with these psycho pharmaceuticals.

  20. Synthesis of dendritic silver nanostructures supported by graphene nanosheets and its application for highly sensitive detection of diazepam

    International Nuclear Information System (INIS)

    Majidi, Mir Reza; Ghaderi, Seyran; Asadpour-Zeynali, Karim; Dastangoo, Hossein

    2015-01-01

    In this paper, preparation, characterization and application of a new sensor for fast and simple determination of trace amount of diazepam were described. This sensor is based on Ag nanodendrimers (AgNDs) supported by graphene nanosheets modified glassy carbon electrode (GNs/GCE). The AgNDs were directly electrodeposited on the surface of electrode via potentiostatic method without using any templates, surfactants, or stabilizers. The structure of the synthesized AgNDs/GNs was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, X-ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS) techniques. The nanodendrimers with tree-like and hierarchical structures have a fascinating structure for fabrication of effective electrocatalysts. The experimental results confirmed that AgNDs/GNs/GC electrode has good electrocatalytic activity toward the reduction of diazepam. A low detection limit of 8.56 × 10 −8 M and a wide linear detection range of 1.0 × 10 −7 to 1.0 × 10 −6 M and 1.0 × 10 −6 to 20 × 10 −6 M were achieved via differential pulse voltammetry (DPV). The proposed electrode displayed excellent repeatability and long-term stability and it was satisfactorily used for determination of diazepam in real samples (commercially tablet, injection and human blood plasma) with high recovery. - Graphical abstract: The typical images for bare GC electrode, GNs/GCE and AgNDs/GNs/GCE and electrocatalytic reduction of diazepam on the surface of modified electrode. - Highlights: • Applying a simple, fast and cost-effective method for synthesis of silver nanodendrimers • Characterization of AgNDs/GNs/GCE surface by SEM, EDX, XRD, EIS and CV methods • Successful application of this sensor for diazepam determination with an excellent detection limit • Calculation of diffusion coefficient, electron transfer coefficient and standard heterogeneous rate constant for diazepam • Satisfactorily using of this

  1. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

    Energy Technology Data Exchange (ETDEWEB)

    Lagard, Camille, E-mail: camille.lagard@gmail.com [Inserm, U1144, Paris (France); UMR-S 1144, Paris-Descartes University, Paris (France); UMR-S 1144, Paris-Diderot University, Paris (France); Chevillard, Lucie, E-mail: luciechevillard@gmail.com [Inserm, U1144, Paris (France); UMR-S 1144, Paris-Descartes University, Paris (France); UMR-S 1144, Paris-Diderot University, Paris (France); Malissin, Isabelle, E-mail: isabellemalissin@gmail.com [Assistance Publique – Hôpitaux de Paris, Lariboisière Hospital, Department of Medical and Toxicological Critical Care, Paris (France); Risède, Patricia, E-mail: patricia.risede@inserm.fr [Inserm, U1144, Paris (France); UMR-S 1144, Paris-Descartes University, Paris (France); UMR-S 1144, Paris-Diderot University, Paris (France); Callebert, Jacques, E-mail: jacques.callebert@aphp.fr [Inserm, U1144, Paris (France); UMR-S 1144, Paris-Descartes University, Paris (France); UMR-S 1144, Paris-Diderot University, Paris (France); Assistance Publique – Hôpitaux de Paris, Lariboisière Hospital, Laboratory of Biochemistry and Molecular Biology, Paris (France); Labat, Laurence, E-mail: laurence.labat@aphp.fr [Inserm, U1144, Paris (France); UMR-S 1144, Paris-Descartes University, Paris (France); UMR-S 1144, Paris-Diderot University, Paris (France); Assistance Publique – Hôpitaux de Paris, Cochin Hospital, Laboratory of Toxicology, Paris (France); Launay, Jean-Marie, E-mail: jean-marie.launay@aphp.fr [Assistance Publique – Hôpitaux de Paris, Lariboisière Hospital, Laboratory of Biochemistry and Molecular Biology, Paris (France); Inserm, U942, Paris (France); and others

    2016-11-01

    Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon–Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P = 0.04). Tramadol induced dose-dependent sedation (P < 0.05), early-onset seizures (P < 0.001) and increase in inspiratory (P < 0.01) and expiratory times (P < 0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P < 0.01) and respiratory depression (P < 0.05) by reducing tidal volume (P < 0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern

  2. Possible involvement of dopamine D-1 and D-2 receptors in diazepam-induced hyperphagia in rats.

    Science.gov (United States)

    Naruse, T; Amano, H; Koizumi, Y

    1991-01-01

    Possible involvement of dopamine receptors in diazepam-induced (1 mg/kg, subcutaneous (sc] hyperphagia was studied in nondeprived rats. Pretreatment with the selective D-1 antagonist, SCH23390 (0.03 mg/kg, sc) inhibited diazepam-induced hyperphagia. In addition, pretreatment with the preferential D-2 antagonists, haloperidol (0.1 to 0.3 mg/kg, sc) and clebopride (0.1 to 0.3 mg/kg, sc) inhibited diazepam-induced hyperphagia in a dose-dependent manner. Pretreatment with co-administration of SCH23390 (0.1 mg/kg, sc) and clebopride (0.03 mg/kg, sc) completely inhibited this hyperphagia. The selective D-2 antagonist, sulpiride (40 mg/kg, sc) and the peripheral D-2 antagonist, domperidone (10 mg/kg, sc) did not affect diazepam-induced hyperphagia. However, sulpiride (10 micrograms, icv) or domperidone (2 micrograms, icv) administered centrally inhibited this hyperphagia. The highest dose of haloperidol (0.3 mg/kg, sc) or clebopride (0.3 mg/kg, sc) and higher doses of SCH23390 (0.01 and 0.03 mg/kg, sc) or SCH23390/clebopride (0.01/0.03 and 0.01/0.1 mg/kg, sc) tended to decrease spontaneous feeding in non-deprived rats. In addition, the highest dose of haloperidol, clebopride or SCH23390/clebopride inhibited spontaneous feeding in deprived rats. Interestingly, diazepam-induced hyperphagia was inhibited significantly by doses of haloperidol (0.1 mg/kg, sc), clebopride (0.1 mg/kg, sc) and SCH23390/clebopride (0.003/0.03 and 0.003/0.1 mg/kg, sc) which did not affect spontaneous feeding in non-deprived or deprived rats. Pretreatment with alpha-methyl-p-tyrosine (40 mg/kg, IP x 2, 6 and 2 h prior to diazepam administration) failed to inhibit this hyperphagia. Furthermore, pretreatment with a large dose of haloperidol (5 mg/kg, sc, 4 days before diazepam administration) augmented the sub-hyperphagic effect to diazepam (0.5 mg/kg, sc). Thus, these findings suggest that hyperphagia to diazepam is mediated in part by both dopamine D-1 and D-2 receptors in non-deprived rats.

  3. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

    International Nuclear Information System (INIS)

    Lagard, Camille; Chevillard, Lucie; Malissin, Isabelle; Risède, Patricia; Callebert, Jacques; Labat, Laurence; Launay, Jean-Marie

    2016-01-01

    Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon–Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P = 0.04). Tramadol induced dose-dependent sedation (P < 0.05), early-onset seizures (P < 0.001) and increase in inspiratory (P < 0.01) and expiratory times (P < 0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P < 0.01) and respiratory depression (P < 0.05) by reducing tidal volume (P < 0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern

  4. Dose related anxiolytic effects of diazepam: relation with serum electrolytes, plasma osmolality and systolic blood pressure (sbp) in rats

    International Nuclear Information System (INIS)

    Farooq, R.; Haleem, D.J.; Haleem, M.A.

    2008-01-01

    Diazepam is an anxiolytic and anticonvulsant drug that also induces hypnosis. Changes in serum electrolyte balance, plasma osmolality and systolic blood pressure (SBP) are often associated with stress-induced anxiety. Administration of diazepam has been show to decrease stress-induced enhancement of hypothalamic pituitary adrenal cortical (HPA) axis. The present is designed to monitor the anxiolytic effects of different doses of diazepam (1 mg/kg, 2.5 mg/kg and 5 mg/kg) and its association with changes of serum electrolyte balance, plasma osmolality and SBP in rats. Administration of diazepam at doses of 1 mg/kg, 2.5 mg/kg and 5 mg/kg elicited anxiolytic effects monitored in light-dark transition test and increased serum concentration of electrolytes and plasma osmolality. Serum levels of magnesium as well as SBP decreased. The results are discussed in context of anxiolytic effects of diazepam to be mediated via a modulation of stress-induced increase in the activity of HPA-axis arid electrolytes balance. (author)

  5. Diazepam administration prevents testosterone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress.

    Science.gov (United States)

    Ruffoli, R; Carpi, A; Giambelluca, M A; Grasso, L; Scavuzzo, M C; Giannessi F, F

    2006-10-01

    Lipofuscin is an autofluorescent and undegradable material, which accumulates in tissues during ageing and under different types of stress. Among these, oxidative stress represents a major trigger for lipofuscin formation. However, prolonged noise exposure is also an effective stressful stimuli. Diazepam may inhibit lipofuscinogenesis in liver and prevent the noise-induced reduction of the steroidogenesis in the adrenal gland. The aim of the study was to ascertain whether chronic noise exposure causes lipofuscin accumulation in mouse testis, and to evaluate the effects of diazepam administration. Eight-week old mice were either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further group was used as control (group C). Light fluorescence and transmission electron microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of group A, which concomitantly had low serum testosterone levels; pre-treatment with diazepam occluded both effects. The present study indicates that: (i) chronic noise exposure causes lipofuscin accumulation at the level of the Leydig cells and a decrease in testosterone; (ii) all these effects are suppressed by pre-treatment with diazepam. As the Leydig cells represent the only cellular type of the interstitial testicular tissue having peripheral benzodiazepine receptors, these results could be explained by the capacity of the peripheral benzodiazepine receptors to prevent reactive oxygen species damage and to increase the resistance of these cells to oxidative stress.

  6. Differential effects of diazepam and MPEP on habituation and neuro-behavioural processes in inbred mice.

    Science.gov (United States)

    Salomons, Amber R; Pinzon, Nathaly Espitia; Boleij, Hetty; Kirchhoff, Susanne; Arndt, Saskia S; Nordquist, Rebecca E; Lindemann, Lothar; Jaeschke, Georg; Spooren, Will; Ohl, Frauke

    2012-06-11

    Previous studies have demonstrated a profound lack of habituation in 129P3 mice compared to the habituating, but initially more anxious, BALB/c mice. The present study investigated whether this non-adaptive phenotype of 129P3 mice is primarily based on anxiety-related characteristics. To test this hypothesis and extend our knowledge on the behavioural profile of 129P3 mice, the effects of the anxiolyticdiazepam (1, 3 and 5 mg/kg) and the putative anxiolytic metabotropic glutamate receptor 5 (mGlu5R) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 3, 10 and 30 mg/kg) treatment on within-trial (intrasession) habituation, object recognition (diazepam: 1 mg/kg; MPEP 10 mg/kg) and on the central-nervous expression of the immediate early gene c-Fos (diazepam: 1 mg/kg; MPEP 10 mg/kg) were investigated. Behavioural findings validated the initially high, but habituating phenotype of BALB/c mice, while 129P3 mice were characterized by impaired intrasession habituation. Diazepam had an anxiolytic effect in BALB/c mice, while in higher doses caused behavioural inactivity in 129P3 mice. MPEP revealed almost no anxiolytic effects on behaviour in both strains, but reduced stress-induced corticosterone responses only in 129P3 mice. These results were complemented by reduced expression of c-Fos after MPEP treatment in brain areas related to emotional processes, and increased c-Fos expression in higher integrating brain areas such as the prelimbic cortex compared to vehicle-treated 129P3 mice. These results suggest that the strain differences observed in (non)adaptive anxiety behaviour are at least in part mediated by differences in gamma-aminobutyric acid- A and mGluR5 mediated transmission.

  7. Effect of breastfeeding piperine on the learning of offspring mice: interaction with caffeine and diazepam.

    Science.gov (United States)

    Moghadamnia, Ali Akbar; Zangoori, Vahid; Zargar-Nattaj, Seyed Sadegh; Tayebi, Pooya; Moghadamnia, Yasaman; Jorsaraei, Seyed Gholam Ali

    2010-01-01

    Piperine, the main alkaloid of black pepper (Piper nigrum), has been suggested to display several pharmacological properties, including pain relief, anticonvulsant, antidepressant-like, antianxiety, sedative, and anti-inflammatory effects. This study was designed to investigate the effect of piperine on learning in mice and the interaction of the effect with caffeine and diazepam. Piperine (100 mg/kg intraperitoneally) was injected into the mouse mothers or nursing dams during breastfeeding for 25 days at five-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task. Mouse learning was assessed 1 hr and 24 hr and 1 week after a training session. Piperine increased learning in the first (1 hr: 243.33 s vs 55.17 s, P = 0.002) and third assessments (1 week: 226 s vs 97 s, P effect of a low dose of caffeine (25 mg/kg intraperitoneally after a shock of 2 s duration) in a first assessment (295.17 s vs 149.17 s, P = 0.026) compared to a higher dose of caffeine. Piperine reversed diazepam (1 mg/kg intraperitoneally) suppression of learning 24 hours after training by a 4 s shock (298 s vs 135.67 s, P = 0.03). According to the results, piperine alone significantly increased learning 1 hour and 1 week after training assessments, and learning can be improved in the short term when followed by piperine administration. It was also shown that piperine can potentiate the effect of a low dose of caffeine and can reverse the effect of diazepam.

  8. Conditioned suppression of sexual behavior in stallions and reversal with diazepam.

    Science.gov (United States)

    McDonnell, S M; Kenney, R M; Meckley, P E; Garcia, M C

    1985-06-01

    Sexual behavior dysfunction unaccompanied by detectable physical or endocrine abnormality is an important cause of reproductive failure among domestic stallions. Several authors have suggested that such dysfunction may be psychogenic, related to negative experience associated with intense handling and training. An experimental model of experience-related dysfunction was developed by exposing pony stallions to erection-contingent aversive conditioning. This resulted in rapid, specific suppression of sexual arousal and response similar to spontaneously occurring dysfunction. Subsequently, treatment with a CNS-active benzodiazepine derivative (diazepam) reversed these effects.

  9. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    DEFF Research Database (Denmark)

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous mod...... have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns...

  10. Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety.

    Science.gov (United States)

    Taukulis, H K; Goggin, C E

    1990-03-01

    On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.

  11. Interaction between diazepam and hippocampal corticosterone after acute stress: impact on memory in middle-aged mice

    Directory of Open Access Journals (Sweden)

    Daniel eBeracochea

    2011-04-01

    Full Text Available Benzodiazepines (BDZ are widely prescribed in the treatment of anxiety disorders associated to aging. Interestingly, whereas a reciprocal interaction between the GABAergic system and HPA axis has been evidenced, there is to our knowledge no direct evaluation of the impact of BDZ on both hippocampus (HPC corticosterone concentrations and HPC-dependent memory in stressed middle-aged subjects. We showed previously that an acute stress induced in middle-aged mice severe memory impairments in a hippocampus-dependent task, and increased in parallel hippocampus corticosterone concentrations, as compared to non stressed middle-aged controls (Tronche et al., 2010. Based on these findings, the aims of the present study were to evidence the impact of diazepam (a positive allosteric modulator of the GABA-A receptor on HPC glucocorticoids concentrations and in parallel on HPC-dependent memory in acutely stressed middle-aged mice.Microdialysis experiments showed an interaction between diazepam doses and corticosterone concentrations into the HPC. From 0.25 mg/kg to 0.5 mg/kg, diazepam dose-dependently reduces intra-HPC corticosterone concentrations and in parallel, dose-dependently increased hippocampal-dependent memory performance. In contrast, the highest (1.0mg/kg diazepam dose induces a reduction in HPC corticosterone concentration, which was of greater magnitude as compared to the two other diazepam doses, but however decreased the hippocampal-dependent memory performance. In summary, our study provides first evidence that diazepam restores in stressed middle-aged animals the hippocampus-dependent response, in relation with HPC corticosterone concentrations. Overall, our data illustrate how stress and benzodiazepines could modulate cognitive functions depending on hippocampus activity.

  12. Effects of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 on amygdaloid kindled seizures and the anticonvulsant efficacy of diazepam.

    Science.gov (United States)

    Albertson, T E; Walby, W F

    1986-11-01

    The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied. When diazepam (3 mg/kg) was injected 15 min before or after a second injection of the vehicle control DMSO (0.25 ml/kg), a significant reduction in the duration of afterdischarge and seizure rank, elicited by a suprathreshold stimulation in amygdaloid-kindled rats, occurred. When either CGS 8216 (10 mg/kg) or RO 15-1788 (10 mg/kg) were given 15 min before diazepam (3 mg/kg) prior to stimulation, the anticonvulsant properties of diazepam were blocked. When RO 15-1788 (10 mg/kg) was given 15 min after diazepam, antagonism of the anticonvulsant effects on diazepam was shown. However, when either CGS-8216 (10 mg/kg) or PK-11195 (10 and 60 mg/kg) were given 15 min after diazepam (3 mg/kg), the anticonvulsant properties of diazepam were not blocked. The anticonvulsant effects of diazepam were reversed when CGS-8216 (10 mg/kg) was given 5 min after diazepam (3 mg/kg) or when a larger dose (30 mg/kg) was given at the same 15 min interval.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. An Efficacy and Pharmacokinetic Evaluation of a Dose of Diazepam That Will Reduce the Incidence of Convulsions in Indian Rhesus Monkeys Pretreated with Pyridostigmine Bromide, Challenged with Soman, and Treated with Atropine and Pralidoxime Chloride with the Diazepam

    Science.gov (United States)

    1990-12-01

    INOIVIDUAL 22b. TELEPKONE (Include Area Code) 22C. OFFICE SYMBOL d "- . t ,-- ian ., - - ,’ ) " :-" D0 Form 1473, JUN 86 Previous editions are obsolete...9) von Bredow, J., Jaax, N., Hayward, I., Wade, J., Maitland , G., and Kaminskis, A., "Estimate of the Lowest Dose of Diazepam Required to Treat

  14. Ketamine anesthesia with or without diazepam premedication for bone marrow punctures in children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Tamminga, RYJ; Noordhoek, M; Kroon, J; Faber-Nijholt, R

    2000-01-01

    Ketamine is a drug widely used for analgesia and sedation of children for diagnostic and therapeutic procedures. The authors investigated in a randomized controlled clinical trial id diazepam premedication would have a beneficial effect on side effects related to ketamine anesthesia for bone marrow

  15. Azone® decreases the buccal mucosal permeation of Diazepam in a concentration-dependent manner via a reservoir effect

    DEFF Research Database (Denmark)

    Meng-Lund, Emil; Jacobsen, Jette; Jin, Liang

    2014-01-01

    The purpose of this study was to examine concentration-dependent effects of Azone® (AZ) on the buccal absorption of diazepam (DIAZ). Porcine buccal mucosa was placed in modified Ussing chambers and pretreated with 10 μL of 0%, 5%, 20%, and 50% (w/v) AZ in ethanol. DIAZ was administered to the don...

  16. Synthesis of dendritic silver nanostructures supported by graphene nanosheets and its application for highly sensitive detection of diazepam

    Energy Technology Data Exchange (ETDEWEB)

    Majidi, Mir Reza, E-mail: sr.majidi@gmail.com; Ghaderi, Seyran; Asadpour-Zeynali, Karim; Dastangoo, Hossein

    2015-12-01

    In this paper, preparation, characterization and application of a new sensor for fast and simple determination of trace amount of diazepam were described. This sensor is based on Ag nanodendrimers (AgNDs) supported by graphene nanosheets modified glassy carbon electrode (GNs/GCE). The AgNDs were directly electrodeposited on the surface of electrode via potentiostatic method without using any templates, surfactants, or stabilizers. The structure of the synthesized AgNDs/GNs was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, X-ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS) techniques. The nanodendrimers with tree-like and hierarchical structures have a fascinating structure for fabrication of effective electrocatalysts. The experimental results confirmed that AgNDs/GNs/GC electrode has good electrocatalytic activity toward the reduction of diazepam. A low detection limit of 8.56 × 10{sup −8} M and a wide linear detection range of 1.0 × 10{sup −7} to 1.0 × 10{sup −6} M and 1.0 × 10{sup −6} to 20 × 10{sup −6} M were achieved via differential pulse voltammetry (DPV). The proposed electrode displayed excellent repeatability and long-term stability and it was satisfactorily used for determination of diazepam in real samples (commercially tablet, injection and human blood plasma) with high recovery. - Graphical abstract: The typical images for bare GC electrode, GNs/GCE and AgNDs/GNs/GCE and electrocatalytic reduction of diazepam on the surface of modified electrode. - Highlights: • Applying a simple, fast and cost-effective method for synthesis of silver nanodendrimers • Characterization of AgNDs/GNs/GCE surface by SEM, EDX, XRD, EIS and CV methods • Successful application of this sensor for diazepam determination with an excellent detection limit • Calculation of diffusion coefficient, electron transfer coefficient and standard heterogeneous rate constant for diazepam

  17. Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture

    International Nuclear Information System (INIS)

    Marinucci, Lorella; Balloni, Stefania; Bodo, Maria; Carinci, Francesco; Pezzetti, Furio; Stabellini, Giordano; Carmela, Conte; Lumare, Eleonora

    2009-01-01

    Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFβ 3 ) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene regulation, so further studies are necessary to determine whether GABAergic system could be involved in the development of diazepam mediated CLP phenotype. Taken together the results elucidate the molecular mechanisms underlying possible toxicology effects induced by diazepam. Counselling of women on the safety of diazepam exposure is clinically important, also for the forensic consequences

  18. Food hoarding, but not food intake, is attenuated by acute diazepam treatment in female Mongolian gerbils (Meriones unguiculatus).

    Science.gov (United States)

    Yang, Hui-Di; Wang, Qian; Wang, De-Hua

    2014-06-01

    This article is part of a Special Issue "Energy Balance". Effects of γ-aminobutyric acid (GABA) on food hoarding are unknown in rodents, and the effects of energy balance and GABA have not been evaluated in females. To evaluate the role of food deprivation and GABA on food hoarding, female Mongolian gerbils were given i.p. injection of diazepam (1mg/kg and 3mg/kg, respectively), a GABAA receptor agonist. Among food-deprived females, there was a bimodal pattern in the frequency of gerbils with different levels of food hoarding. High food hoarding (HFH) and low food hoarding (LFH) gerbils were analyzed. Diazepam blocked food deprivation-induced food hoarding in HFH gerbils, but not in LFH gerbils. This blockade was associated with increased cellular activation in selected brain areas, such as the nucleus accumbens (NAcc), caudate putamen (CP) and ventral tegmental area (VTA), which suggested that direct activation of GABA in the brain reward circuitry decreased food hoarding in HFH females. Moreover, diazepam increased Fos expression in field CA2 and CA3 of the hippocampus, but had no significant effect on Fos expression in field CA1 and dentate gyrus (DG) of the hippocampus, indicating that the hippocampus has area-specific effects on food hoarding in HFH gerbils. Diazepam did not alter food intake in both HFH and LFH gerbils. In addition, serum corticosterone concentrations were higher in the HFH than in the LFH ones. Together, these data indicated that food deprivation increased food hoarding in female gerbils, diazepam reduced food deprivation-induced food hoarding in HFH gerbils, and that GABA might influence food hoarding via classical reward circuitry via the mesolimbic dopamine system and specific hippocampal areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

    Science.gov (United States)

    Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

    2012-03-17

    Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Sedative effect of oral diazepam and chloral hydrate in the dental treatment of children

    Directory of Open Access Journals (Sweden)

    Kantovitz Kamila

    2007-06-01

    Full Text Available Purpose : The purpose was to evaluate two sedation protocols during dental sessions in anxious children. Materials and Methods : It was a randomized and double-blind study, with each individual being his/her own control within each protocol. Furthermore, the two protocols were compared. Twenty children (36 to 84 months old who exhibited "definitely negative" behavior according to the Frankl scale were assigned to receive oral chloral hydrate (40 mg/kg (Group I or Diazepamβ (5 mg (Group II. Behavior during local anesthesia, application of rubber dam, cavity preparation, restorative procedures was evaluated, considering the degree of sleep, body movement, crying and overall behavior. Vital signs were assessed at three different times. The Wilcoxon, Mann-Whitney, Exact Fisher′s and Spearman correlation tests were used to analyze the data. Results : Group I presented higher scores for sleep during the CH session than placebo session during rubber dam application ( P = 0.0431 and restoration ( P = 0.0431. In Group II there was no statistically significant difference ( p > 0.05. There were no statistically significant differences between sessions and groups in the evaluation of body movement, crying and vital signs. Overall behavior in the placebo session was better than in the CH session during local anesthesia, but there was no difference between the two drug regimens. There was influence of age during anesthesia and cavity preparation in Group I and during rubber dam application in Group II. It was concluded that oral diazepam and chloral hydrate had no influence on the behavior management for dental treatment with the studied sample.

  1. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    OpenAIRE

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

  2. Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose

    OpenAIRE

    Đorđević Snežana; Jović-Stošić Jasmina; Kilibarda Vesna; Šegrt Zoran; Perković-Vukčević Nataša

    2016-01-01

    Backgound/Aim. Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylli...

  3. Pregnenolone biosynthesis in C6-2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor.

    OpenAIRE

    Papadopoulos, V; Guarneri, P; Kreuger, K E; Guidotti, A; Costa, E

    1992-01-01

    The C6-2B glioma cell line, rich in mitochondrial receptors that bind with high affinity to benzodiazepines, imidazopyridines, and isoquinolinecarboxamides (previously called peripheral-type benzodiazepine receptors), was investigated as a model to study the significance of the polypeptide diazepam binding inhibitor (DBI) and the putative DBI processing products on mitochondrial receptor-regulated steroidogenesis. DBI and its naturally occurring fragments have been found to be present in high...

  4. Study on sedative effects of different fractions of Hop (Humulus lupulus L. extract compared with diazepam in rats

    Directory of Open Access Journals (Sweden)

    R Shishehgar

    2012-05-01

    Full Text Available Humulus lupulus is a medicinal plant which in Farsi is called "razak". The purpose of this research is, studying the sedative effects of polar, semi polar and non polar fractions extracted from Hop (Humulus lupulus. L in comparison with diazepam in the animal model of Rat. For conducting this research polar, semi polar and non polar fractions extracted from Hop based on the polarity of solvent. Then study continued with the injection of obtained extracts and other medicines to different groups of Wistar breed of rats. First group was injected with 100mg/kg of Polar fraction extract the second group, with 100mg/kg of Semipolar extract, the third group, with 100 mg/kg of non-polar extract of Humulus lupulus the fourth group with 2 mg/kg of Diazepam the fifth group with the same volume of DMSO used as solvent of injectable medicines an the sixth group was the control group and did not receive any drug. The method of injection was Intra peritoneal (IP form. Statistical diagrams and results showed a significant decreasing of anesthetic induction time and increasing of sleeping time of Ketamin induced anesthesia, after IP injection of the Polar fraction extract of Humulus lupulus. The results obtained showed that the polar-fraction extract of Humulus lupulus has more sufficient sedative effects than diazepam and other under studied groups.

  5. Anesthetic efficacy of ketamine-diazepam, ketamine-xylazine, and ketamine-acepromazine in Caspian Pond turtles (Mauremys caspica).

    Science.gov (United States)

    Adel, Milad; Sadegh, Amin Bigham; Arizza, Vincenzo; Abbasi, Hossein; Inguglia, Luigi; Saravi, Hasan Nasrollahzadeh

    2017-01-01

    The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles ( Mauremys caspica ). Three groups of the Caspian Pond turtles ( n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine-diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine-acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine-xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly. The onset times of anesthetization and the recovery time were measured. Statistical analysis of the data was performed using one-way analysis of variance followed by t -tests, and P turtles, respectively, compared to that obtained with the ketamine-acepromazine combination and 64% (male turtles) and 50% (female turtles) shorter than that obtained with the ketamine-xylazine combination. Further, the recovery time, in male turtles, was 17% shorter in animals treated with the first drug combination than those treated with the ketamine-acepromazine combination and 37% shorter than those treated with the ketamine-xylazine combination. The recovery time, in female turtles, did not seem to be significantly different among treatments. The study showed that the ketamine-diazepam drug combination is the anesthetic combination with the fastest onset time and shortest recovery time.

  6. Anticonvulsant action of gamma-irradiated diazepam with correlation to certain brain amino acids and electrocorticogram activity in experimental animals

    International Nuclear Information System (INIS)

    Saad, S.F.; Roushdy, H.M.; Hassan, S.H.M.; Elkashef, H.S.; Mahdy, A.M.; Elsayeh, B.M.

    1994-01-01

    The effect of sterilization by gamma irradiation (215 KGy) of diazepam on is anticonvulsant action, on norma and depleted cerebral gamma aminobutyric acid (GABA), on glutamic acid, as well as electrocorticogram activity (ECOG) was determined in the experimental animals. For the evaluation of the anticonvulsant action of either diazepam (D) or irradiated diazepam (ID), pentyl ene tetrazole seizure test, was used and the protective dose 50 (PD50) was determined in adult male mice. GABA, the main central inhibitory transmitter which is implicated in the mechanism of the anticonvulsant action of D and its precursor glutamic acid, were electrophoretically separated and spectrophotometrical evaluated. Moreover, brain electrical activity was recorded using an electroencephalograph apparatus. Although the PD50 of ID as well the effect on normal brain cerebral GABA and glutamic acids did not differ significantly from that of D, yet there was certain variabilities. Thus, the effect of D was about 4 times more potent than the ID on elevating depleted cerebral GABA. Also, electrocorticogram records demonstrated that D produced a slight inhibition while ID induced a decrease in B rhythm with remarkable in the amplitude of ECOG waves. The same pattern of effects were obtained when D or ID were used in combination with INH (250 mg kg-1). 1 tab. 1 fig

  7. A comparative study of sedative and anxiolytic effects of the Hypericum perforatumin and diazepam on rats

    Directory of Open Access Journals (Sweden)

    Ali Rezaei

    2012-01-01

    Full Text Available Background: Hypericum perforatum or St. John’s wort is a plant known as a Raee flower (or Hypericum in Persian. Hyperisin and Hyperforin are the main constituents of this plant extract that are connected to sigma opioid and GABA receptors. Its various pharmacological effects, such as analgesia, sedation, anti-spasm, anti-convulsion, anti-anxiety, and anti-bacteria have already been known. Materials and Method: To conduct the study, the authors prepared the hydro alcohol extract taken from the aerial organ of the plant. Then, different groups of female Wistar rats, which were almost equal in age and weight, received doses of 500mg/kg and 250mg/kg of the extract, 1.2mg/kg of diazepam, and di-methyl solphoxid (as placebo with equal volumes. The intraperitoneal injections were administered 15min before assessing the sedative/hypnotic effects (i.e. duration of the induced sleep by ketamin with a dose of 40mg/kg and the anxiolytic effects by means of the elevated plus maze.Results: The results showed a statistically significant increase (p= 0.00 both in the duration of the induced sleep by ketamin and in the time lapsed in the open arms in the experimental groups with high and low doses of the extract.Conclusion: The findings suggest that the extract of Hypericum perforatum with a dose of 500mg/kg could have sedative, preanaesthetic, and anxiolytic effects.

  8. Regional GABA concentration and [3H]-diazepam binding in rat brain following repeated electroconvulsive shock

    International Nuclear Information System (INIS)

    Bowdler, J.M.; Green, A.R.; Minchin, M.C.W.; Nutt, D.J.

    1983-01-01

    It has been confirmed that 24 hours following a series of electroconvulsive shocks (ECS) given once daily for 10 days (ECS x 10) to rats there is an increase in GABA concentration in the corpus striatum. A similar change was seen after the ECS had been given to rats anaesthetised with halothane, or when 5 ECS were given spread out over 10 days, the rats being anaesthetised during the ECS. A daily convulsion for 10 days elicited by flurothyl exposure resulted in an increased striatal GABA concentration, but also increased the GABA concentration in the hypothalamus, hippocampus and cortex. The increase in striatal GABA concentration was present 24 hours after ECS daily for 5 days or 3 days after ECS daily for 10 days. No change in [ 3 H]-diazepam binding was seen in hippocampus, cortex or corpus striatum 24 hours after the last of 10 once daily ECS. The increase in striatal GABA concentration was therefore seen at all times when enhanced monoaminemediated behaviours have been demonstrated following seizures. (Author)

  9. Physical and behavioral development in rats after late prenatal exposure to diazepam.

    Science.gov (United States)

    Lall, S B; Sahoo, R N

    1990-01-01

    The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

  10. Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose.

    Science.gov (United States)

    Djordjević, Snezana; Jović-Stosić, Jasmina; Kilibarda, Vesna; Segrt, Zoran; Perković-Vukcević, Natasa

    2016-02-01

    Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2:1 ratio) applied as concomitant therapy. Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS) in single ionmonitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column usingthe mixture of acidic acetonitrile and 20 mM of ammonium acetatein water (55 : 45) as a mobile phase. The applied analitycal method showed excellent recovery (94.65%). The obtained extracts were much cleaner than the extracts obtained by the sameextractant in the process of liquid-liquid extraction. The limit ofdetection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In the patientstreated with both flumazenil and aminophylline

  11. Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2016-01-01

    Full Text Available Backgound/Aim. Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2 : 1 ratio applied as concomitant therapy. Methods. Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS in single ion monitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column using the mixture of acidic acetonitrile and 20 mM of ammonium acetate in water (55 : 45 as a mobile phase. Results. The applied analitycal method showed excellent recovery (94.65%. The obtained extracts were much cleaner than the extracts obtained by the same extractant in the process of liquid-liquid extraction. The limit of detection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In

  12. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

    Science.gov (United States)

    Apland, James P.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Pidoplichko, Volodymyr I.; Rossetti, Katia

    2018-01-01

    The currently Food and Drug Administration–approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe—depending on the region—in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. PMID:29467308

  13. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population.

    Science.gov (United States)

    Apland, James P; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Pidoplichko, Volodymyr I; Rossetti, Katia; Braga, Maria F M

    2018-05-01

    The currently Food and Drug Administration-approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABA A receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD 50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe-depending on the region-in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. U.S. Government work not protected by U.S. copyright.

  14. The use of ketamine plus diazepam anaesthesia to increase the radiosensitivity of a C3H mouse mammary adenocarcinoma in hyperbaric oxygen

    International Nuclear Information System (INIS)

    Tozer, G.M.; Penhaligon, M.; Nias, A.H.W.

    1984-01-01

    The radiation response of mammary tumours transplanted into syngeneic C3H mice has been measured with the animals breathing air or 100% oxygen at 290 kPa (HPO), either with or without ketamine plus diazepam anaesthesia. The single doses needed to cure 37% of tumours within 40 days (TCDsub(37/40)) for mice anaesthetised with ketamine plus diazepam and for unanaesthetised mice irradiated in air were not significantly different, 66.5 Gy and 68.8 Gy respectively. When animals were irradiated in HPO, the TCD 37 value was significantly reduced from 60 Gy with no anaesthetic to 41 Gy with ketamine plus diazepam anaesthesia; an enhancement ratio (ER) of 1.5. The total ER from no anaesthetic in air to anaesthetic in HPO was 1.7 (68.8/41). There was less CNS toxicity for ketamine plus diazepam than for sodium pentobarbitone anaesthesia in mice treated in HPO. The combination of ketamine and diazepam is an unusual anaesthetic in that it maintains blood pressure, cardiac output and respiration in man. Vascular effects and lowered body and tumour temperatures may also have influenced tumour oxygenation and radiation response. (author)

  15. Effects of xylazine, medetomidine, detomidine, and diazepam on sedation, heart and respiratory rates, and cloacal temperature in rock partridges (Alectoris graeca).

    Science.gov (United States)

    Uzun, Metehan; Onder, Feyyaz; Atalan, Gultekin; Cenesiz, Metin; Kaya, Mehmet; Yildiz, Sedat

    2006-06-01

    In this study, heart and respiratory rates, cloacal temperature, and quality of sedation were evaluated before (0 min) and after (10, 20, and 30 min) i.m. administration of xylazine (10 mg/kg; n = 7), medetomidine (75 li; n = 6), detcmidine (0.3 mg/kg; n = 6), or diazepam (6 mg/kg; n = 7) in rock partridges (Alectoris graeca). All partridges recovered from sedation without any disturbance. Xylazine and diazepam administration did not induce significant changes in heart rate, which did decrease significantly after medetomidine and detomidine administration (P detomidine injection (P detomidine, 2.6 +/- 0.4 min for diazepam, 3.1 -+/-.4 min for xylazine, and 4.8+/-0.8 min for medetomidine application. There was an extreme variability in time to recovery for each drug: 205 +/-22.2 min for xylazine, 95 -12.2 min for medetomidine, 260+/-17.6 min for detomidine, and 149 + 8.3 min for diazepam. In conclusion, xylazine, medetomidine, detomidine, and diazepam produced sedation, which could permit some clinical procedures such as handling and radiographic examination of partridges to occur. Of the four drugs, xylazine produced stronger and more efficient sedation compared to the others, which could permit only minor procedures to be performed. However, depending on the drug used, monitoring of heart and respiratory rates and cloacal temperature might be required.

  16. Behavioral effects of diazepam in the murine plus-maze: flumazenil antagonism of enhanced head dipping but not the disinhibition of open-arm avoidance.

    Science.gov (United States)

    Dalvi, A; Rodgers, R J

    1999-04-01

    Although it is widely believed that benzodiazepines reduce anxiety through positive allosteric modulation of the GABA(A)-chloride channel complex, this is not the only mechanism through which agents of this class can modify CNS function. Furthermore, a significant number of reports of apparent flumazenil blockade of diazepam anxiolysis in animal models have paid limited attention to possible intrinsic behavioral actions of the antagonist per se. In the present study, ethological methods were employed to assess in detail the effects of diazepam, flumazenil, and their combination on the behavior of male DBA/2 mice in the elevated plus-maze paradigm. In two experiments, diazepam (1.5 mg/kg) alone reduced open-arm avoidance and increased head dipping, whereas flumazenil (10-40 mg/kg) alone was without significant behavioral effect. However, with the sole exception of head dipping, prior administration of flumazenil (10 and 40 mg/kg) failed to block the behavioral effects of diazepam under present test conditions. These findings imply that the anxiolytic effects of diazepam in the mouse plus-maze are not mediated through flumazenil-sensitive benzodiazepine receptors and that alternate mechanisms must be considered.

  17. Differential effects of MPEP and diazepam in tests of conditioned emotional response and Pavlovian-to-instrumental transfer suggests 'anxiolytic' effects are mediated by different mechanisms.

    Science.gov (United States)

    George, S A; Hutson, P H; Stephens, D N

    2009-06-01

    The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is reported to be anxiolytic in several animal models of anxiety, including the conditioned emotional response (CER) paradigm. Suppression of responding during conditioned stimulus (CS) presentation in CER may reflect behavioural competition between lever pressing and adopting a shock-avoidance posture, or it may alternatively reflect altered value of the food reward following its association with a footshock, thus reducing its ability to motivate responding. If this is the case, then drugs that reduce the CER may interfere with the mechanism by which CSs are able to motivate responding, rather than by reducing anxiety. The standard test of the ability of Pavlovian cues to motivate responding is the Pavlovian-to-instrumental transfer (PIT) paradigm and it has recently been suggested that CER may be 'negative PIT'. We compared the effect of MPEP (0, 3, 10 and 30 mg/kg) and diazepam (0, 1, 3 and 10 mg/kg) in CER and PIT. Both MPEP and diazepam significantly reduced conditioned suppression in the CER paradigm. MPEP, but not diazepam, significantly reduced PIT. The findings support the hypothesis that MPEP may reduce expression of anxiety in the CER paradigm by interfering with the way in which emotionally salient cues are able to affect behaviour, but do not support such an analysis of the effect of diazepam. Diazepam and MPEP may therefore achieve their effects in CER by influencing different psychological processes.

  18. Effects of buspirone, diazepam, and zolpidem on open field behavior, and brain [3H]muscimol binding after buspirone pretreatment.

    Science.gov (United States)

    Siemiatkowski, M; Sienkiewicz-Jarosz, H; Członkowska, A I; Bidziński, A; Płaźnik, A

    2000-07-01

    The effects of 5-HT(1A) receptor agonist buspirone, a nonselective (diazepam), and a selective (zolpidem) GABA(A) receptor agonist were compared in the open field test of neophobia. Unhabituated rats were pretreated with the drugs once, prior to a first exposure to the open field, and their behavior was recorded both during this test and during a second trial 24 h later. It has been hypothesized that the decrease in exploratory activity observed during the second test session may be considered an adaptive reaction to the first day aversive experience (neophobia). If so, a selective modulation of 5-HT and GABA systems activity during the test could bring about significant changes in animal behavior on the retest. Buspirone at the lowest dose of 0.3 mg/kg revealed anxiolytic-like properties on the first day, whereas the action of diazepam and zolpidem was modulated by the dose-related sedative effect. At the dose of 2.4 mg/kg buspirone elicited delayed in time anxiolytic-like action, i.e., produced the antithigmotactic effect during the retrial 24 h later. Diazepam and zolpidem failed to exhibit similar profile of action. Autoradiography of [3H]muscimol binding after pretreatment of rats with buspirone showed a significant increase in the selective radioligand binding within the frontal cortex and a similar, near-significant tendency in the dentate gyrus of the hippocampus. The behavioral data validate buspirone as important drug for the treatment of anxiety disorders, devoid of disruptive influence on motor and cognitive processes. The open field test, as modified by us, appeared sensitive in distinguishing the behavioral profiles of action of different anxiolytic compounds, including 5-HT(1A) receptor agonist. The present results support the assumption that reduced turnover of 5-HT due to stimulation of 5-HT(1A) autoreceptors, may bring about changes in GABA(A) receptor system activity, in some brain structures, leading to the anxiolytic effect.

  19. Comparison of the effects of lavender and diazepam on the anxiety level of patients before orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Javad Shahinfar

    2016-03-01

    Full Text Available Background: Waiting for surgery is one of the stressful environmental factors for each patient. The anxiety caused by waiting could have adverse effects on the patient treatment and recovery process. Given the complications caused by the management of anxiety through pharmaceutical methods, the application of complementary medicine is of paramount importance. This study aimed to compare the effects of lavender and diazepam on the anxiety level of the patients before orthopedic surgery. Methods: This clinical trial was conducted on the patients undergoing orthopedic surgery, who referred to one of the teaching hospitals of Bojnord, Iran, in 2015. In total, 60 patients were selected through randomized convenience sampling and divided into the intervention and control groups. The intervention group received 300 mg of lavender extract, whereas the control group orally consumed diazepam 5 mg prior to the surgery. The anxiety level of the patients was measured one night and one hour before the surgery using the Spielberger’s State-Trait Anxiety Inventory. The data analysis was performed in the SPSS version 16, using the paired sample t-test, Fisher’s exact test, Chi-square test, and independent t-test. Results: According to the results of the present study, the mean anxiety level of the intervention group varied from 9.8±6.0 to 76.2±5.5 (P<0.001 after the intervention. On the other hand, the mean anxiety level of the participants of the control group decreased from 100.0±5.5 to 80.0±5.7 (P<0.001. However, this difference was not statistically significant between the two groups. Conclusion: As the findings indicated, similar to diazepam, the lavender can diminish the anxiety level in the patients before the orthopedic surgery. It is recommended to use the lavender before the surgeries to decrease the anxiety level since the herbal medicine is associated with less complications, compared to the diazepam.

  20. Extraction, separation, and detections of 14C-diazepam and 14C-metabolites from brain tissue of mature and old rats

    International Nuclear Information System (INIS)

    Komiskey, H.L.; Rahman, A.; Weisenburger, W.P.; Hayton, W.L.; Zobrist, R.H.; Silvius, W.

    1985-01-01

    A rapid method for simultaneous determination of brain concentrations of diazepan and each of its three major metabolites in brain tissue by a reverse isotope dilution procedure is presented. Radiolabeled diazepam and metabolites were extracted from brain tissue of mature and senescent rats with ethyl ether. After the ether was evaporated the benzodiazepines were separated from the residue by passing the water soluble portion through C-18 bonded-phase extraction columns. High pressure liquid chromatography (HPLC) was used to separate the benzodiazepines from each other. Reverse isotope dilution analysis was used to quantify diazepam and its metabolites. The percent recovery of diazepam and its metabolites from the brain of mature or senescent rats did not vary significantly

  1. Silexan, an essential oil from flowers of Lavandula angustifolia, is not recognized as benzodiazepine-like in rats trained to discriminate a diazepam cue.

    Science.gov (United States)

    Silenieks, Leo B; Koch, Egon; Higgins, Guy A

    2013-01-15

    Recently, an essential oil of selected quality produced from the flowering tops of Lavandula angustifolia Mill. by steam distillation (Silexan) has been approved in Germany for the treatment of restlessness in case of anxious mood. Based on the observed clinical effects, it has been speculated that lavender oil may exert benzodiazepine-like action including the known dependence and abuse potential of this class of drugs. Although no evidence for such an activity was generated during the long-standing medicinal use of lavender oil, further preclinical investigations were now conducted to evaluate this potential side effect in more detail. Twelve adult, male, Sprague-Dawley rats were trained to discriminate the benzodiazepine drug diazepam (2 mg/kg i.p.) from saline using a two-lever operant procedure. After approximately 40 training sessions the majority of rats learned the discrimination and pre-treatment with ascending doses of diazepam (0.3-2 mg/kg i.p.) produced a dose related generalization to the diazepam cue. In these same animals Silexan was administered to see if animals recognized the drug as "diazepam-like" i.e. generalized to diazepam or "saline-like". Silexan tested at doses 3-30 mg/kg i.p. produced almost exclusively (>90%) saline-like responding. Also there was no effect of Silexan on response rate, i.e. rate of lever pressing, at any dose suggesting that the test article is well tolerated and does not exert a sedating effect. In sum, Silexan has no diazepam-like interoceptive property in adult, male rats. This suggests that Silexan does not share the potential of benzodiazepines to induce the development of tolerance, dependence and addiction. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Non-invasive in situ identification and band assignments of diazepam, flunitrazepam and methadone hydrochloride with FT-near-infrared spectroscopy.

    Science.gov (United States)

    Ali, Hassan Refat H

    2011-03-20

    Near-infrared spectroscopy (NIR) has evolved into an important rapid, direct and non-invasive technique in drugs analysis. In this study, the suitability of NIR spectroscopy to identify two benzodiazepine derivatives, diazepam and flunitrazepam, and a synthetic opiate, methadone hydrochloride, inside USP vials and probe the solid-state form of diazepam presents in tablets has been explored. The results show the potential of NIR spectroscopy for rapid, in situ and non-destructive identification of drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice

    DEFF Research Database (Denmark)

    Budry, Lionel; Bouyakdan, Khalil; Tobin, Stephanie

    2016-01-01

    . Male and female ACBP(GFAP) KO and ACBP KO mice do not show significant changes in anxiety-like behaviour compared to control littermates during elevated plus maze (EPM) and open field (OF) tests. Surprisingly, ACBP(GFAP) KO and ACBP KO mice were unresponsive to the anxiolytic effect of a low dose...... of diazepam during EPM tests. In conclusion, our experiments using genetic ACBP loss-of-function models suggest that endozepines deficiency does not affect anxiety-like behaviour in mice and impairs the anxiolytic action of diazepam....

  4. Comparative study of Valeriana Officinalis root extract¸diazepam and ketamin on CNS depressive effects in cats

    Directory of Open Access Journals (Sweden)

    R Kaffashi Elahi

    2012-02-01

    Full Text Available Valeriana officinalis is a medicinal plant used in alternative medicine for its sedative and anxiolytic properties. It acts trough GABA receptors increases GABA in synaptic space and stimulates GABA receptors. Ketamine and diazepam also acts trough GABA mechanism but with a different pathway. The purpose of our study was to investigate the sedative effects on cats of valerian extract that extremely beloved by cats in combination with ketamine, and evaluate the possibility of its usage in cats and change the routine methods of anti-anxiety and restraining method. 24 healthy short haired mature male cats randomly selected, fed with standard ration and water ad libitum , were divided into three groups G1, G2, G3, received ketamine(11mg/kg, ketamine-diazepam(1mg/kg, and ketamine-valerian (1250 µg/kg PO respectively. Rate of CNS depression were evaluated by; onset time of effects, peak score, and duration of peak score, total time of effects and highest recorded score. Scores obtained by ataxia, time at which falling recumbent and pinch test over anus, tail and Achilles tendon. This experiment was conducted as blind. Statistical analysis made by variance analysis (ANOVA and Tukey test, at a significance level of 5% (p

  5. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    Science.gov (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (Pnootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (Pnootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  6. Study of sedative, preanaesthetic and anxiolytic effects of herbal extract of Lavandula stoechas in comparison with diazepam in rat

    Directory of Open Access Journals (Sweden)

    A Rezaie

    2010-11-01

    Full Text Available Lavandula stoechas grows naturally in most parts of the world specifically south France, the Mediterranean region and Torento. The plant has various pharmacological properties including analgesic, anti-inflammatory, antidepressant, hypnotic, sedative and tranquilizer, muscle relaxant, anticonvulsant, antibacterial and antispasmodic. For studying the effectiveness of sedative, preanesthetic and anxiolytic effects of Lavandula  stoechas in comparison with diazepam different groups of female Wistar rats with the same age and weight conditions received intraperitoneal injections of Lavandula  stoechas (100, 200, 400 mg/kg, ip, diazepam (1.2 mg/kg, ip, dimethyl sulfoxide (DMSO as a placebo with equal volume 30 minutes before assessing the sedative and preanesthetic effects (induced sleep duration by ketamine, 40 mg/kg, ip and anxiolytic effects (using Elevated plus maze and (Rotarod test. Statistical analysis of the results obtained represent a significant increase in sleep time induced with ketamine and also a significant increase in the time the rats spent in open arms of maze with high and low doses of Lavandula stoechas herbal extract (p

  7. Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.

    Science.gov (United States)

    Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

    2014-10-01

    Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures. Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam (5 and 10mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Δ(9)-THC. These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons.

    Directory of Open Access Journals (Sweden)

    Sergiy V Korol

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diazepam. In whole-cell recordings in rat brain slices, diazepam (1 μM, an allosteric positive modulator of GABAA receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABAA current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM plus diazepam (1 μM, only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diazepam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABAA receptors in the CA3 pyramidal neurons.

  9. Comparison of surgical conditions following premedication with oral clonidine versus oral diazepam for endoscopic sinus surgery: A randomized, double-blinded study

    Directory of Open Access Journals (Sweden)

    Rohini V Bhat Pai

    2016-01-01

    Full Text Available Background and Aims: Endoscopic sinus surgery (ESS provides a challenge and an opportunity to the anesthesiologists to prove their mettle and give the surgeons a surgical field which can make their delicate surgery safer,more precise and faster. The aim of the study was to evaluate the surgical field and the rate of blood loss in patients premedicated with oral clonidine versus oral diazepam for endoscopic sinus surgery. Material and Methods: ASA I or II patients who were scheduled to undergo ESS were randomly allocated to group D (n = 30 or group C (n = 30. The patients′ vital parameters, propofol infusion rate, and rate of blood loss were observed and calculated. The surgeon, who was blinded, rated the visibility of the surgical field from grade 0-5. Results: In the clonidine group, the rate of blood loss, the surgical time, propofol infusion rate was found to be statistically lower as compared to the diazepam group. Also a higher number of patients in the clonidine group had a better surgical score (better surgical field than the diazepam group and vice versa. Conclusions: Premedication with clonidine as compared to diazepam, provides a better surgical field with less blood loss in patients undergoing ESS.

  10. Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products and in-silico toxicological assessment.

    Science.gov (United States)

    Carpinteiro, Inmaculada; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2017-09-01

    In this work, the reaction of four benzodiazepines (diazepam, oxazepam, nordazepam and temazepam) during water chlorination was studied by means of liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOF-MS). For those compounds that showed a significant degradation, i.e. diazepam, oxazepam and nordazepam, parameters affecting to the reaction kinetics (pH, chlorine and bromide level) were studied in detail and transformation products were tentatively identified. The oxidation reactions followed pseudofirst-order kinetics with rate constants in the range of 1.8-42.5 M -1  s -1 , 0.13-1.16 M -1  s -1 and 0.04-20.4 M -1  s -1 corresponding to half-life values in the range of 1.9-146 min, 1.8-87 h and 2.5-637 h for oxazepam, nordazepam and diazepam, respectively, depending of the levels of studied parameters. Chlorine and pH affected significantly the reaction kinetics, where an increase of the pH resulted into a decrease of the reaction rate, whereas higher chlorine dosages led to faster kinetics, as expected in this case. The transformation of the studied benzodiazepines occurs mainly at the 1,4-diazepine 7-membered-ring, resulting in ring opening to form benzophenone derivatives or the formation of a 6-membered pyrimidine ring, leading to quinazoline derivatives. The formation of these by-products was also tested in real surface water samples observing kinetics of oxazepam degradation slower in river than in creek water, while the degradation of the two other benzodiazepines occurred only in the simpler sample (creek water). Finally, the acute and chronical toxicity and mutagenicity of precursors and transformation products were estimated using quantitative structure-activity relationship (QSAR) software tools: Ecological Structure Activity Relationships (ECOSAR) and Toxicity Estimation Software Tool (TEST), finding that some transformation products could be more toxic/mutagenic than the precursor drug, but additional test would be needed

  11. Preparation of a novel sorptive stir bar based on vinylpyrrolidone-ethylene glycol dimethacrylate monolithic polymer for the simultaneous extraction of diazepam and nordazepam from human plasma.

    Science.gov (United States)

    Torabizadeh, Mahsa; Talebpour, Zahra; Adib, Nuoshin; Aboul-Enein, Hassan Y

    2016-04-01

    A new monolithic coating based on vinylpyrrolidone-ethylene glycol dimethacrylate polymer was introduced for stir bar sorptive extraction. The polymerization step was performed using different contents of monomer, cross-linker and porogenic solvent, and the best formulation was selected. The quality of the prepared vinylpyrrolidone-ethylene glycol dimethacrylate stir bars was satisfactory, demonstrating good repeatability within batch (relative standard deviation < 3.5%) and acceptable reproducibility between batches (relative standard deviation < 6.0%). The prepared stir bar was utilized in combination with ultrasound-assisted liquid desorption, followed by high-performance liquid chromatography with ultraviolet detection for the simultaneous determination of diazepam and nordazepam in human plasma samples. To optimize the extraction step, a three-level, four-factor, three-block Box-Behnken design was applied. Under the optimum conditions, the analytical performance of the proposed method displayed excellent linear dynamic ranges for diazepam (36-1200 ng/mL) and nordazepam (25-1200 ng/mL), with correlation coefficients of 0.9986 and 0.9968 and detection limits of 12 and 10 ng/mL, respectively. The intra- and interday recovery ranged from 93 to 106%, and the relative standard deviations were less than 6%. Finally, the proposed method was successfully applied to the analysis of diazepam and nordazepam at their therapeutic levels in human plasma. The novelty of this study is the improved polarity of the stir bar coating and its application for the simultaneous extraction of diazepam and its active metabolite, nordazepam in human plasma sample. The method was more rapid than previously reported stir bar sorptive extraction techniques based on monolithic coatings, and exhibited lower detection limits in comparison with similar methods for the determination of diazepam and nordazepam in biological fluids. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    International Nuclear Information System (INIS)

    Vito, Stephen T.; Austin, Adam T.; Banks, Christopher N.; Inceoglu, Bora; Bruun, Donald A.; Zolkowska, Dorota; Tancredi, Daniel J.; Rogawski, Michael A.; Hammock, Bruce D.; Lein, Pamela J.

    2014-01-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA A R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA A R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA A R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase inhibitor alters

  13. Influence of a Double-Lumen Extension Tube on Drug Delivery: Examples of Isosorbide Dinitrate and Diazepam.

    Directory of Open Access Journals (Sweden)

    Aurélie Maiguy-Foinard

    Full Text Available Plastic materials such as polyurethane (PUR, polyethylene (PE, polypropylene (PP and polyvinyl chloride (PVC are widely used in double-lumen extension tubing. The purposes of our study were to 1 compare in vitro drug delivery through the double extension tubes available on the market 2 assess the plastic properties of PUR in infusion devices and their impact on drug delivery.The study compared eight double-lumen extension tubes in PUR, co-extruded (PE/PVC plastic and plasticised PVC from different manufacturers. Isosorbide dinitrate and diazepam were used as model compounds to evaluate their sorption on the internal surface of the infusion device. Control experiments were performed using norepinephrine known not to absorb to plastics. Drug concentrations delivered at the egress of extension tubes were determined over time by an analytical spectrophotometric UV-Vis method. The main characteristics of plastics were also determined.Significant differences in the sorption phenomenon were observed among the eight double-lumen extension tubes and between pairs of extension tubes. Mean concentrations of isosorbide dinitrate delivered at the egress of double-lumen extension tubes after a 150-minute infusion (mean values ± standard deviation in percentage of the initial concentrations in the prepared syringes ranged between 80.53 ± 1.66 (one of the PUR tubes and 92.84 ± 2.73 (PE/PVC tube. The same parameters measured during diazepam infusion ranged between 48.58 ± 2.88 (one of the PUR tubes and 85.06 ± 3.94 (PE/PVC tube. The double-lumen extension tubes in PUR were either thermosetting (resin or thermoplastic according to reference.Clinicians must be aware of potential drug interactions with extension tube materials and so must consider their nature as well as the sterilisation method used before selecting an infusion device.

  14. Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study

    Directory of Open Access Journals (Sweden)

    Ilić Nela V.

    2012-01-01

    Full Text Available Introduction. Administration of pharmacological agents with specific actions on neurotransmitter systems is a powerful driver of functional cortical reorganization. Plastic reorganization of the motor cortex in humans studies by the use of non-invasive stimulation protocols, which mimic the Hebbian model of associative plasticity. Objective. Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level. Methods. We analyzed effects of benzodiazepines (10 mg, levodopa (200 mg and placebo on PAS protocol in 14 healthy volunteers, using a double-blind placebo-controlled study design. PAS consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the scalp (transcranial magnetic stimulation in precisely defined intervals (ISI was 10 and 25 ms for a total of about 15 minutes (200 pairs. MEP amplitudes before and after (0, 10, 20 and 30 minutes later interventional protocols were compared. Results. When protocols were applied with placebo depending on ISI (10 ms - inhibitory, 25 ms - facilitatory effects, MEP amplitudes decreased or increased, while values in the postinterventional period (0, 10, 20 and 30 min were compared with initial values before the use of SAS. The use of benzodiazepines caused the occlusion of LTP-like effect, in contrast to amplification effects recorded after the administration of levodopa. With respect to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p<0.001. Conclusion. Administration of GABA-ergic agonist diazepam interferes with the induction of associative plasticity in the motor cortex of healthy individuals, as opposed to the use of levodopa, which stimulates these processes. The observed effects point at a

  15. Barriers to publishing in biomedical journals perceived by a sample of French researchers: results of the DIAzePAM study.

    Science.gov (United States)

    Duracinsky, Martin; Lalanne, Christophe; Rous, Laurence; Dara, Aichata Fofana; Baudoin, Lesya; Pellet, Claire; Descamps, Alexandre; Péretz, Fabienne; Chassany, Olivier

    2017-07-10

    As publishing is essential but competitive for researchers, difficulties in writing and submitting medical articles to biomedical journals are disabling. The DIAzePAM (Difficultés des Auteurs à la Publication d'Articles Médicaux) survey aimed to assess the difficulties experienced by researchers in the AP-HP (Assistance Publique - Hôpitaux de Paris, i.e., Paris Hospitals Board, France), the largest public health institution in Europe, when preparing articles for biomedical journals. The survey also aimed to assess researchers' satisfaction and perceived needs. A 39-item electronic questionnaire based on qualitative interviews was addressed by e-mail to all researchers registered in the AP-HP SIGAPS (Système d'Interrogation, de Gestion et d'Analyse des Publications Scientifiques) bibliometric database. Between 28 May and 15 June 2015, 7766 researchers should have received and read the e-mail, and 1191 anonymously completed the questionnaire (write (79%) or submit (27%), limited skills in English (40%) or in writing (32%), and difficulty in starting writing (35%). 87% of respondents would accept technical support, especially in English reediting (79%), critical reediting (63%), formatting (52%), and/or writing (41%), to save time (92%) and increase high-impact-factor journal submission and acceptance (75%). 79% of respondents would appreciate funding support for their future publications, for English reediting (56%), medical writing (21%), or publication (38%) fees. They considered that this funding support could be covered by AP-HP (73%) and/or by the added financial value obtained by their department from previous publications (56%). The DIAzePAM survey highlights difficulties experienced by researchers preparing articles for biomedical journals, and details room for improvement.

  16. Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    H. Milani

    1999-10-01

    Full Text Available In the central nervous system, magnesium ion (Mg2+ acts as an endogenous modulator of N-methyl-D-aspartate (NMDA-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg, either alone or in combination with diazepam (DZ, on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc in single (1x, 2 h post-ischemia or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia. DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34, DZ (10 mg/kg, N = 24, MgCl2 (2.5 mmol/kg, N = 10, MgCl2 (5.0 mmol/kg, N = 17, MgCl2 (7.5 mmol/kg, N = 9 or MgCl2 (5 mmol/kg + DZ (10 mg/kg, N = 14. Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3% and CA1 (88.4% sectors of the hippocampus (P0.05. Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05. No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.

  17. Anticonvulsant activity of methanolic extract from Kalanchoe pinnata Lam. stems and roots in mice: A comparison to diazepam.

    Science.gov (United States)

    Mora-Pérez, A; Hernández-Medel, M del R

    2016-04-01

    In ancient and current traditional medicine in México, extracts from the leaves or whole plant of 'life leaf' (Kalanchoe pinnata [K. pinnata]Lam) have been used to treat an entity known locally as 'yellow epilepsy' (alferecía amarilla) when it is accompanied by seizures. However, the anticonvulsive activity of its stems and roots remains unexplored The anticonvulsant activity of the methanolic root extract (MER) or stem (MES) of K. pinnata Lam. was evaluated in a pentylenetetrazol-induced seizure model in Balb/C mice, and effects were compared to those of diazepam. The stem extract fractions that produced anticonvulsant activity were subsequently evaluated using the pentylenetetrazol -induced seizure model. We observed increased latency of tonic-clonic seizures that was inversely proportional to the dose of MRE, with a similar impact on the lethal effects of pentylenetetrazol. Different doses of the MSE showed a dose-dependent increase in latency to myoclonus, clonus, and tonic-clonic seizures, acting similarly to diazepam and offering 100% protection against the lethal effects of pentylenetetrazol. Fractioning MSE decreased its effectiveness, but when fractions were mixed with fractions of chloroform and ethyl acetate, anticonvulsive activity was restored. The preliminary phytochemical analysis identified alkaloids and sterols in MRE, and sterols and terpenes in MSE CONCLUSIONS: The anticonvulsant activity of K. pinnata Lam. decreases with increased doses of MRE, whereas the effect of MSE is dose-dependent and preserved in the mixture chloroform and ethyl acetate. We suggest that the metabolites responsible for these effects are sterols in MRE, and sterols and terpenes in MSE. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  18. The redox behaviour of diazepam (Valium®) using a disposable screen-printed sensor and its determination in drinks using a novel adsorptive stripping voltammetric assay.

    Science.gov (United States)

    Honeychurch, Kevin C; Crew, Adrian; Northall, Hannah; Radbourne, Stuart; Davies, Owian; Newman, Sam; Hart, John P

    2013-11-15

    In this study we investigated the possibility of applying disposable electrochemical screen-printed carbon sensors for the rapid identification and quantitative determination of diazepam in beverages. This was achieved utilising a previously unreported oxidation peak. The origin of this peak was investigated further by cyclic voltammetry and gas chromatography/mass spectroscopy. At pH 6 the voltammetric behaviour of this oxidation process was found to involve adsorption of the drug allowing for the development of an adsorptive stripping voltammetric assay. Experimental conditions were then optimised for the determination of diazepam in a beverage sample using a medium exchange technique. It was shown that no elaborate extraction procedures were required as the calibration plots obtained in the absence and presence of the beverage were very similar. © 2013 Elsevier B.V. All rights reserved.

  19. Centrosome structure and function is altered by chloral hydrate and diazepam during the first reproductive cell cycles in sea urchin eggs

    Science.gov (United States)

    Schatten, H.; Chakrabarti, A.

    1998-01-01

    This paper explores the mode of action of the tranquillizers chloral hydrate and diazepam during fertilization and mitosis of the first reproductive cell cycles in sea urchin eggs. Most striking effects of these drugs are the alteration of centrosomal material and the abnormal microtubule configurations during exposure and after recovery from the drugs. This finding is utilized to study the mechanisms of centrosome compaction and decompaction and the dynamic configurational changes of centrosomal material and its interactions with microtubules. When 0.1% chloral hydrate or 350-750 microM diazepam is applied at specific phases during the first cell cycle of sea urchin eggs, expanded centrosomal material compacts at distinct regions and super-compacts into dense spheres while microtubules disassemble. When eggs are treated before pronuclear fusion, centrosomal material aggregates around each of the two pronuclei while microtubules disappear. Upon recovery, atypical asters oftentimes with multiple foci are formed from centrosomal material surrounding the pronuclei which indicates that the drugs have affected centrosomal material and prevent it from functioning normally. Electron microscopy and immunofluorescence studies with antibodies that routinely stain centrosomes in sea urchin eggs (4D2; and Ah-6) depict centrosomal material that is altered when compared to control cells. This centrosomal material is not able to reform normal microtubule patterns upon recovery but will form multiple asters around the two pronuclei. When cells are treated with 0.1% chloral hydrate or 350-750 microM diazepam during mitosis, the bipolar centrosomal material becomes compacted and aggregates into multiple dense spheres while spindle and polar microtubules disassemble. With increased incubation time, the smaller dense centrosome particles aggregate into bigger and fewer spheres. Upon recovery, unusual irregular microtubule configurations are formed from centrosomes that have lost their

  20. Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

    Science.gov (United States)

    Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

    2018-04-01

    In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Biomimetic synthesis of proline-derivative templated mesoporous silica for increasing the brain distribution of diazepam and improving the pharmacodynamics of nimesulide

    DEFF Research Database (Denmark)

    Li, Heran; Wang, Jianxin; Cong, Jialiang

    2017-01-01

    Herein a new kind of proline-derivative templated mesoporous silica with curved channels (CMS) was biomimetically synthesized and applied as carrier to improve the drug dissolution and bioavailability of hydrophobic diazepam (DZP) and nimesulide (NMS). Drugs can be incorporated into CMS with high...... improved, and the inhibition rates of 1:3 NMS/CMS in all pharmacodynamics tests varied from 102.2% to 904.3%....

  2. The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302

    Science.gov (United States)

    2014-11-01

    to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the cur- rent US Food and Drug... status epilepticus (SE), which are initiated by the excessive stimulation of cholinergic receptors. If immediate death is prevented by adequate...5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid; PBS, phosphate-buffered saline; SE, status epilepticus ; UBP302, (S)-3-(2-carboxybenzyl

  3. Barriers to publishing in biomedical journals perceived by a sample of French researchers: results of the DIAzePAM study

    Directory of Open Access Journals (Sweden)

    Martin Duracinsky

    2017-07-01

    Full Text Available Abstract Background As publishing is essential but competitive for researchers, difficulties in writing and submitting medical articles to biomedical journals are disabling. The DIAzePAM (Difficultés des Auteurs à la Publication d’Articles Médicaux survey aimed to assess the difficulties experienced by researchers in the AP-HP (Assistance Publique – Hôpitaux de Paris, i.e., Paris Hospitals Board, France, the largest public health institution in Europe, when preparing articles for biomedical journals. The survey also aimed to assess researchers’ satisfaction and perceived needs. Methods A 39-item electronic questionnaire based on qualitative interviews was addressed by e-mail to all researchers registered in the AP-HP SIGAPS (Système d’Interrogation, de Gestion et d’Analyse des Publications Scientifiques bibliometric database. Results Between 28 May and 15 June 2015, 7766 researchers should have received and read the e-mail, and 1191 anonymously completed the questionnaire (<45 years of age: 63%; women: 55%; physician: 81%; with PhD or Habilitation à Diriger des recherches––accreditation to direct research––: 45%. 94% of respondents had published at least one article in the previous 2 years. 76% of respondents felt they were not publishing enough, mainly because of lack of time to write (79% or submit (27%, limited skills in English (40% or in writing (32%, and difficulty in starting writing (35%. 87% of respondents would accept technical support, especially in English reediting (79%, critical reediting (63%, formatting (52%, and/or writing (41%, to save time (92% and increase high-impact-factor journal submission and acceptance (75%. 79% of respondents would appreciate funding support for their future publications, for English reediting (56%, medical writing (21%, or publication (38% fees. They considered that this funding support could be covered by AP-HP (73% and/or by the added financial value obtained by their

  4. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    International Nuclear Information System (INIS)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

    2012-01-01

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA A ) receptors. However, seizure activity itself causes the endocytosis of GABA A receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD 50 ; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an

  5. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A., E-mail: lucille.a.lange@us.army.mil

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was

  6. Investigating Sedative, Preanaesthetic & Anti-anxiety Effects of Herbal Extract of Cannabis Sativa in Comparison with Diazepam in Rats

    Directory of Open Access Journals (Sweden)

    A rezaei

    2014-04-01

    Full Text Available Introduction: Cannabis sativa is a plant that is Called Cannabis in Persian and has diversity all over the world. This plant grows in North region, Arak and Kashan in Iran. Chemical compounds of this plant are cannabidiol, cannabidiolic acid and tetra hydro cannabinol that cause the increase in duration of anesthesia via injection of anesthesia drugs. This effect shows the effectiveness of this plant extraction for sedation and smoothing. It is claimed that the usage of this drug for preanesthesia causes the reduction of anesthesia duration induction and increases anesthesia persistency. It seems that Cannabis and its compounds have effects on sleep through hypothalamus and posterior nucleus hemisphere. Methods: herbal extract of Cannabis Sativa (with doses of 150, 300, 450mg/kg, IP, Diazepam (with dose of 1.2mg/kg, IP, and Di-methyl sulphoxide with the equal volume was injected intraperitoneally into two different groups of male wistar rats 30 minutes before assessing the relief sedative and preanaesthetic effects (induced sleep duration by ketamine 40mg/kg, ip & anti-anxiety effects (using elevated plus maze. Results: The results showed a meaningful increase in the period of the sleep time that had been induced with Ketamine and also a meaningful increase was observed in the time spent at open arms in the treatment groups with high and low dose of extract. Conclusion: The results showed that the Cannabis Sativa extract with dose of 350mg/kg has sedative, preanaesthetic & anti-anxiety effects.

  7. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Vito, Stephen T., E-mail: stvito@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Austin, Adam T., E-mail: aaustin@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Inceoglu, Bora, E-mail: abinceoglu@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Bruun, Donald A., E-mail: dabruun@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Zolkowska, Dorota, E-mail: dzolkowska@gmail.com [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Tancredi, Daniel J., E-mail: djtancredi@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Rogawski, Michael A., E-mail: rogawski@ucdavis.edu [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States)

    2014-12-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase

  8. Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage

    Energy Technology Data Exchange (ETDEWEB)

    Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio [Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612 (United States); Auta, James [Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612 (United States)

    2009-02-27

    Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at {alpha}1- but is a high efficacy positive allosteric modulator at {alpha}5-containing GABA{sub A} receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5

  9. Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage

    International Nuclear Information System (INIS)

    Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio; Auta, James

    2009-01-01

    Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at α1- but is a high efficacy positive allosteric modulator at α5-containing GABA A receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a

  10. Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

    Science.gov (United States)

    Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E

    2017-07-01

    Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Gerenciamento de resíduos oriundos da fabricação e distribuição do medicamento Diazepam para o município de São Mateus, ES Management of residues deriving from the manufacture and distribution of Diazepam in the city of São Mateus, ES

    Directory of Open Access Journals (Sweden)

    Elda Falqueto

    2008-04-01

    Full Text Available O presente trabalho se propôs a estudar o gerenciamento de resíduos de um medicamento de uso controlado. O Diazepam, por ser importante na terapêutica e amplamente utilizado, além de ter seu uso controlado pela Vigilância Sanitária, foi o medicamento de escolha para este estudo. Observou-se a geração de resíduos desde a fabricação do Diazepam até sua distribuição, bem como o tratamento e destinação final dos resíduos. O estudo teve início num município de médio porte, do estado do Espírito Santo, chamado São Mateus. No Brasil, 27,6% dos municípios, de forma semelhante a São Mateus, são de médio porte e contam com a presença de um serviço municipal de vigilância sanitária acoplado a um serviço de meio ambiente. O estudo, que é de caráter qualitativo, teve como objetivos: identificar os principais tipos de resíduos do medicamento Diazepam; estudar as principais causas que levam à geração do Diazepam resíduo; estudar as dificuldades no gerenciamento dos resíduos sólidos pelos atores envolvidos neste processo; estudar a legislação ambiental/sanitária relacionada e seu emprego. As relações entre estas atividades e os órgãos responsáveis pela fiscalização e controle destes resíduos, principalmente no que diz respeito ao cumprimento das regulamentações, também fizeram parte do trabalho.This work aimed to study the management of residues of a controlled prescription drug. Diazepam was the drug chosen for this study for its therapeutic importance and wide use, and for being a prescription drug controlled by the National Health Surveillance Agency - ANVISA. The generation of residues of Diazepam from manufacture to distribution as well as the management and final destination of these residues was observed. The study started in an average-size city in the state of Espírito Santo, called São Mateus. In Brazil, 27.6% of cities are medium-sized like São Mateus and count on the presence of a municipal

  12. Solubility of clonazepam and diazepam in binary and ternary mixtures of polyethylene glycols 400 or 600, propylene glycol and water at 298.2K - experimental data and modeling

    Directory of Open Access Journals (Sweden)

    Bastami Zahra

    2014-01-01

    Full Text Available Experimental molar solubilities of clonazepam and diazepam in binary and ternary mixtures of polyethylene glycols (PEGs 400 or 600, propylene glycol (PG and water (138 data points along with the density of the saturated solutions at 298.2K were reported. The Jouyban-Acree model was used to fit to the measurements for providing a computational method. Employing the solubilities in the mono-solvents, the measured solubilities in mixed solvents were back-calculated and the overall mean percentage deviations (OMPDs of the model were 16.0 % and 19.2% for diazepam and clonazepam, respectively. Addition of the Hansen solubility parameters to the model helps us to train all the data sets (clonazepam and diazepam at once and the back-calculated OMPD for this analysis was 19.3%.

  13. Curcumin Reverses the Diazepam-Induced Cognitive Impairment by Modulation of Oxidative Stress and ERK 1/2/NF-κB Pathway in Brain

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    Alexandra C. Sevastre-Berghian

    2017-01-01

    Full Text Available Oxidative stress and inflammation can be involved in cognitive dysfunction associated with neurodegenerative disorders. Diazepam (DZP administration has been chosen to simulate the memory impairment. The aim of this study was to evaluate the effects of curcumin (CUR on spatial cognition, ambulatory activity, and blood and brain oxidative stress levels. The ERK/NF-κB signaling pathway and the histopathological changes in the hippocampus and frontal lobe, in diazepam-treated rats, were also analyzed. The animals were divided into 4 groups: control, carboxymethylcellulose (CMC + CUR, CMC + DZP, and CUR + CMC + DZP. CUR (150 mg/kg b.w. was orally administered for 28 days. DZP (2 mg/kg b.w. was intraperitoneally administered 20 minutes before the behavioral tests (open field test, Y-maze, and elevated plus maze. CUR improved the spontaneous alternation behavior, decreased the oxidative stress levels, both in the blood and in the hippocampus, and downregulated the extracellular signal-regulated kinase (ERK 1/2/nuclear transcription factor- (NF- κB/pNF-κB pathway in the hippocampus and the iNOS expression in the hippocampus and frontal lobe of the DZP-treated rats. Histopathologically, no microscopic changes were found. The immunohistochemical signal of iNOS decreased in the DZP and CUR-treated group. Thus, our findings suggest that curcumin administration may improve the cognitive performance and may also have an antioxidant effect.

  14. Study of sedative preanaesthetic and anxiolytic effects of herbal extract of Tilia platyphyllos scop in comparison with diazepam in the rat

    Directory of Open Access Journals (Sweden)

    A Rezaie

    2011-05-01

    Full Text Available Tilia platyphyllos scop belongs to the Tiliaceae family and mainly grows in northern parts of the country. It has various pharmacological effects including anxiolytic, antibacterial, anticonvulsant, spasmolytic, tranquilization and sedation, hypnotic and muscular relaxation. In order to study sedative, preanaesthetic and anxiolytic effects herbal extract of Tiliaplatyphyllos scop in comparison with diazepam in different groups of female Wistar rats with the same age and weight, doses of 150 mg/kg, 300 mg/kg and  450 mg/kg of herbal extract, 1.2 mg/kg of diazepam and equal volumes of dimethyl sulfoxide as a placebo were injected to rats intraperitoneally 30 minutes prior to evaluation of sedative and preanaesthetic effects (induced sleep duration following 40 mg/kg administration intraperitoneally and anxiolytic effects (using elevated plus maze and Rotarod test. Statistical results obtained represent a significant increase in sleep time induced with ketamine and also a significant increase in time spent by rats in open arms of maze with high and low doses of Tiliaplatyphyllos scop herbal extract (p

  15. Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives.

    Science.gov (United States)

    Auta, J; Romeo, E; Kozikowski, A; Ma, D; Costa, E; Guidotti, A

    1993-05-01

    The 2-hexyl-indoleacetamide derivative, FGIN-1-27 [N,N-di-n-hexyl-2- (4-fluorophenyl)indole-3-acetamide], and the imidazopyridine derivative, alpidem, both bind with high affinity to glial mitochondrial diazepam binding inhibitor receptors (MDR) and increase mitochondrial steroidogenesis. Although FGIN-1-27 is selective for the MDR, alpidem also binds to the allosteric modulatory site of the gamma-aminobutyric acidA receptor where the benzodiazepines bind. FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions. The anti-isoniazid convulsant action of FGIN-1-27 and alpidem, but not that of THDOC, is blocked by PK 11195. In contrast, flumazenil blocked completely the anticonvulsant action of clonazepam and zolpidem and partially blocked that of alpidem, but it did not affect the anticonvulsant action of THDOC and FGIN-1-27. Alpidem, like clonazepam, zolpidem and diazepam, but not THDOC or FGIN-1-27, delay the onset of bicuculline-induced convulsions. In two animal models of anxiety, the neophobic behavior in the elevated plus maze test and the conflict-punishment behavior in the Vogel conflict test, THDOC and FGIN-1-27 elicited anxiolytic-like effects in a manner that is flumazenil insensitive, whereas alpidem elicited a similar anxiolytic effect, but is partially blocked by flumazenil. Whereas PK 11195 blocked the effect of FGIN-1-27 and partially blocked alpidem, it did not affect THDOC in both animal models of anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 125I-iomazenil binding shows stress- and/or diazepam-induced reductions in mouse brain. Supporting data for 123I-iomazenil SPECT study of anxiety disorders

    International Nuclear Information System (INIS)

    Takahashi, Makoto; Odano, Ikuo; Fujita, Shozo; Ohkubo, Masaki.

    1997-01-01

    Effects of repeated swim stress on the binding of 125 I-iomazenil were examined in the brains of diazepam-treated and non-treated mice. The mice were orally administered diazepam or vehicle (0.5% ethylene glycol) and subjected to daily swim stress (at 20degC for 10 min) for seven consecutive days. The distribution and the amount of 125 I-iomazenil binding were analyzed autoradiographically after in vivo and in vitro binding experiments. Repeated swim stress decreased the in vivo binding in the hippocampus (p 125 I-iomazenil binding. These results suggest that we can investigate the pathophysiology of stress and anxiety with 123 I-iomazenil SPECT. Care must be taken concerning the effects of benzodiazepines. (author)

  17. The effect of Coriandrum sativum seed extract on the learning of newborn mice by electric shock: interaction with caffeine and diazepam

    Directory of Open Access Journals (Sweden)

    Seyed Sadegh Zargar-Nattaj

    2011-01-01

    Full Text Available Seyed Sadegh Zargar-Nattaj1, Pooya Tayyebi1, Vahid Zangoori1, Yasaman Moghadamnia4, Hasan Roodgari2, Seyed Gholamali Jorsaraei3, Ali Akbar Moghadamnia11Department of Pharmacology, 2Department of Medical Genetics, 3Department of Anatomical Sciences and Embryology, Babol University of Medical Sciences, Babol, Iran; 4Department of Physics, Alzzahra University, Tehran, IranAbstract: Coriander has been recommended for the relief of pain, anxiety, flatulence, and loss of appetite. In traditional medicine, it is believed that coriander can induce some degree of amnesia in a child when his/her mother uses coriander during the pregnancy. We evaluated the effect of Coriandrum sativum seed extract on learning in second-generation mice. Ethanolic extract (2% of coriander (100 mg/kg intraperitoneal was dissolved in sunflower oil (oil as a vehicle and injected into the control group mother mice during breastfeeding for 25 days at 5-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task with 0.4 mA electric shock for 2 or 4 seconds. While coriander extract showed a negative effect in the short term (1 hour after the training session, it potentiated the mice's learning in later assessments (24 hours post-training [P = 0.022] and 1 week post-training [P = 0.002] by a 4-second shock. Low-dose caffeine (25 mg/kg ip after training improved the learning after 1 hour (P = 0.024; while diazepam (1 mg/kg ip suppressed learning at all time points after the 4-second shock training (1 hour, P = 0.022; 24 hours, P = 0.002; and 1 week, P = 0.008. No modification in the pain threshold was elicited by electric stimuli both in coriander and control groups. In conclusion, coriander does not improve learning within a short period of time after training; however, learning after coriander administration can be improved in the long term.Keywords: Coriandrum sativum, caffeine, diazepam, learning, memory, step through

  18. Functional and morphological effects of diazepam and midazolam on tumor vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility contrast MRI: a comparative study

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    Yan N

    2017-10-01

    Full Text Available Nuo Yan,1 Yuzhen Zheng,2 Cheng Yang1 1Second Department of Anesthesiology, The Affiliated Hospital to Logistics University of PAP, Tianjin, 2Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin, China Abstract: Antiangiogenic therapy attenuates tumor growth by reducing vascularization. Diazepam (DZP and midazolam (MZL have antiangiogenic properties in human umbilical vein endothelial cells. Thus, we investigated the antiangiogenic activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic resonance imaging with gradient-echo (GE and spin-echo (SE to assess perfusion parameters, including cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and mean vessel diameter. The GE-normalized CBF (nCBF in the tumors of untreated controls was significantly lower than that in normal brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had higher CBF and lower CBV and MTT values than did untreated controls. The tumor size decreased significantly to 33.5% in DZP-treated rats (P<0.001 and 22.5% in MZL-treated rats (P<0.01 relative to controls. The SE-normalized CBV was lower in DZP-treated (32.9% and MZL-treated (10.6% rats compared with controls. The mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9% in MZL-treated rats compared with controls (P<0.01. The GE and SE nCBF values were higher in DZP-treated (49.9% and 40.1%, respectively and MZL-treated (41.2% and 32.1%, respectively rats than in controls. The GE- and SE-normalized MTTs were lower in DZP-treated (48.2% and 59.8%, respectively and MZL-treated (40.5% and 51.2%, respectively rats than in controls. Both DZP and MZL had antiangiogenic effects on tumor perfusion and vasculature; however, the antiangiogenic activity of DZP is more promising than that of MZL. Keywords: diazepam, midazolam, 9L gliosarcoma

  19. A silica fiber coated with a ZnO-graphene oxide nanocomposite with high specific surface for use in solid phase microextraction of the antiepileptic drugs diazepam and oxazepam.

    Science.gov (United States)

    Alizadeh, Reza; Salami, Maryam; Seidi, Shahram

    2018-06-02

    A novel ZnO-graphene oxide nanocomposite was prepared and is shown to be a viable coating on fused silica fibers for use in solid phase microextraction (SPME) of diazepam and oxazepam from urine, this followed by thermal desorption and gas chromatographic quantitation using a flame ionization detector. A central composite design was used to optimize extraction time, salt percentage, sample pH and desorption time. Limits of detection are 0.5 μg·L -1 for diazepam and 1.0 μg·L -1 for oxazepam. Repeatability and reproducibility for one fiber (n = 4), expressed as the relative standard deviation at a concentration of 50 μg·L -1 , are 8.3 and 11.3% for diazepam, and 6.7 and 10.1% for oxazepam. The fiber-to-fiber reproducibility is Graphical abstract A hydrothermal method was introduced for preparation of ZnO- GO nano composite on a fused silica fiber as solid phase microextraction with high mechanical, chemical stability and long service life.

  20. A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

    Science.gov (United States)

    D'Mello, G D; Duffy, E A; Miles, S S

    1985-01-01

    A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

  1. Comparative effects of melatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart rate measured by radiotelemetry in Wistar rats.

    Science.gov (United States)

    Mailliet, F; Galloux, P; Poisson, D

    2001-08-01

    The role of melatonin (MLT) in mediating the sleep-wake cycle has been previously suspected of indicating that this substance could be a candidate for a new generation of hypnotics. We investigated whether MLT acted as a sleep promoter or a modulator of sleep temporal timing related to cardiovascular and body temperature (Tb) adaptations to sleep induction. The pharmacological effects of MLT on sleep were compared with zolpidem (ZP) and diazepam (DZ). The radiotelemetry system was used to record the electrocorticogram [slow wave sleep (SWS), paradoxical sleep (PS)], Tb, blood pressure and heart rate in six Wistar rats. DZ (3 mg/kg and 6 mg/kg), ZP (1, 3, 5 and 10 mg/kg) and MLT (2.5 and 5 mg/kg) were delivered intraperitoneally during light (L) and dark (D) periods. MLT increased the number of sleep cycles (L: 30%, D: 110%) and total duration (P<0.05) of PS (L: 70%, D: 150%). In return, ZP (10 mg/kg) presented no effect during L but increased total (40%) and mean duration (37%) of SWS during the D period. DZ modified mean duration of SWS (L: -27%, D: +26%) and increased total duration of SWS (+47%). ZP and DZ induced a more pronounced decrease in Tb than MLT but only DZ induced tachycardia and hypertension. We showed that MLT could not promote sleep and its cardiovascular adaptations despite hypothermia, but modulated the period of ultradian sleep cycles. DZ and ZP promoted sleep and induced hypothermia during the D period. Only DZ disrupted sleep architecture and induced adverse effects on cardiovascular parameters.

  2. Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

    Directory of Open Access Journals (Sweden)

    Breitling Rainer

    2004-03-01

    Full Text Available Abstract Background Zellweger syndrome (ZS is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. Hypothesis We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. Testing the hypothesis Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A agonists during pregnancy. Implications of the hypothesis We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome.

  3. Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

    Directory of Open Access Journals (Sweden)

    Romain eNardou

    2011-07-01

    Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

  4. Combined Diazepam and MK-801 Therapy Provides Synergistic Protection from Tetramethylenedisulfotetramine-induced Tonic-Clonic Seizures and Lethality in Mice

    Science.gov (United States)

    Shakarjian, Michael P.; Ali, Mahil S.; Velíšková, Jana; Stanton, Patric K.; Heck, Diane E.; Velíšek, Libor

    2015-01-01

    The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl− channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 hour lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or

  5. Sensitive, automatic method for the determination of diazepam and its five metabolites in human oral fluid by online solid-phase extraction and liquid chromatography with tandem mass spectrometry

    DEFF Research Database (Denmark)

    Jiang, Fengli; Rao, Yulan; Wang, Rong

    2016-01-01

    A novel and simple online solid-phase extraction liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of diazepam and its five metabolites including nordazepam, oxazepam, temazepam, oxazepam glucuronide, and temazepam glucuronide...... in human oral fluid. Human oral fluid was obtained using the Salivette(®) collection device, and 100 μL of oral fluid samples were loaded onto HySphere Resin GP cartridge for extraction. Analytes were separated on a Waters Xterra C18 column and quantified by liquid chromatography with tandem mass...

  6. Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts

    Directory of Open Access Journals (Sweden)

    Carlos Geraldo Sobral de Medeiros

    2004-06-01

    Full Text Available OBJETIVO: Avaliar o efeito, na contratilidade miocárdica e no fluxo coronariano, de drogas comumente utilizadas na prática clínica (diazepam, midazolam, propofol e etomidato. MÉTODO: Foram estudados 50 corações isolados de ratos Wistar divididos em cinco grupos de dez, em preparação de Langendorff com líquido de perfusão de Krebs-Henseleit (K-H, mantendo-se constantes a pressão de perfusão (90 centímetros de água e a temperatura (37° + 0,5 graus Celsius. Com exceção do Grupo I (Controle, foram feitas infusões únicas, em um minuto, de diazepam (50 microgramas - Grupo II; midazolam (25 microgramas - Grupo III; propofol (25 e 50 microgramas - Grupo IV e etomidato (25 microgramas - Grupo V. Cada dose foi diluída e administrada em 0,1 mililitro de K-H, mantendo-se o fluxo e a pressão de perfusão coronarianos do sistema, durante sua infusão. Aferiu-se a freqüência cardíaca em batimentos por minuto (BPM, a tensão miocárdica em gramas (g, e o fluxo coronariano em mililitros por minuto (ml/min em 1, 3, 5, 10, 15, 20, 25 e 30 minutos; a contratilidade miocárdica foi avaliada pelo cálculo da primeira derivada tensão/tempo (dT/dtmax, naquelas marcas. RESULTADOS: A freqüência cardíaca apresentou variações nos Grupos I, III e IV. Em relação à tensão miocárdica, apenas o Grupo I não sofreu declínio; o fluxo coronariano, exceto no Grupo IV, apresentou variações para menos, ao longo do estudo; a contratilidade miocárdica decresceu em todos os grupos estudados, exceto no Grupo I. CONCLUSÃO: As drogas ensaiadas diminuíram a contratilidade miocárdica (p0,05.OBJECTIVE: The effects on myocardial contractility (dT/dtmax and coronary blood flow (CBF of common drugs used in clinical practice (diazepam, midazolam, propofol and etomidate were studied. METHOD: Fifty Wistar rat's hearts were divided into five groups of ten, and perfused by Langendorff method with Krebs-Henseleit solution (K-H, with the perfusion pressure

  7. The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice.

    Science.gov (United States)

    Reddy, D S; Kulkarni, S K

    1998-06-01

    The present studies were undertaken to investigate the neuroactive steroidal modulation of feeding behavior and possible involvement of gamma-aminobutyric acid type-A (GABA-A) and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) in food-deprived male mice. Allopregnanolone (0.5-2 mg/kg), a neurosteroid, progesterone (1-10 mg/kg), a neurosteroid precursor, and 4'-chlordiazepam (0.25-1 mg/kg), a specific high affinity MDR agonist, produced a dose-dependent hyperphagic effects. In contrast, neurosteroids pregnenolone sulfate (PS) (1-10 mg/kg) and dehydroepiandrosterone sulfate (DHEAS) (1-10 mg/kg) produced a hypophagic effect, in a dose-dependent manner. The allopregnanolone-, progesterone- and 4'-chlordiazepam-induced hyperphagic effect was blocked by picrotoxin (1 mg/kg), a GABA-A chloride channel antagonist, but not by flumazenil (2 mg/kg), a benzodiazepine (BZD) antagonist. The 4'-chlordiazepam-induced hyperphagic effect was prevented by pretreatment with PK11195 (2 mg/kg), a selective partial MDR antagonist. The hypophagic effect of DHEAS (10 mg/kg) was reversed by dizocilpine (10 microg/kg), an NMDA receptor antagonist, but resistant to muscimol (0.1 mg/kg), a selective GABA-A receptor agonist. In contrast, the PS (10 mg/kg)-induced hypophagic response was resistant to dizocilpine, but sensitive to muscimol (0.1 mg/kg). Both the sulfated neurosteroids PS and DHEAS also reversed the hyperphagic effect of allopregnanolone. In addition, the BZD agonist triazolam (0.05-0.25 mg/kg) also produced a flumazenil- and picrotoxin-sensitive hyperphagic effects, thereby suggesting the changes in feeding behavior by neurosteroids represent GABA-A receptor mediated hyperphagic action. Although the possible antistress or anxiolytic actions of neurosteroids may confound the hyperphagia, behavioral effects observed were specific to food because the mice were adopted to the test environment and diet, and of a possible variation between various neurosteroids in the

  8. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.

    2001-01-01

    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

  9. Diazepam e nordiazepam em plasma: métodos de extração líquido-líquido e em fase sólida no pré-tratamento de amostras para análise cromatográfica em fase líquida Diazepam and nordiazepam in plasma: liquid-liquid and solid phase extraction in sample pre-treatment for high performance liquid chromatography analysis

    Directory of Open Access Journals (Sweden)

    Ellen Figueiredo Freire

    2005-10-01

    Full Text Available Analysis of diazepam (DZP and its active metabolite nordiazepam (NDZP in plasma is commonly performed in clinical medicine to ensure proper therapeutic effects while minimizing the incidence of toxicity. This study aimed to optimize analytical parameters and compare two pre-treatment techniques, liquid-liquid (LLE and solid phase extraction (SPE, as well as liquid chromatographic conditions to analyze simultaneously DZP and NDZP in plasma from 20 patients treated with a daily dose of 10 mg. Both techniques showed to be well in line with the international criteria for analytical validation, which permitted to quantify DZP (66.2 - 1148.6 ng mL-1 and NDZP (138.5 - 808.6 ng mL -1 in all samples. The correlation coefficients between SPE and LLE were respectively 0.9729 for DZP and 0.9643 for NDZP.

  10. Synthesis of [[sup 123]I]tert-Butyl 8-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiaze pine 3-carboxylate, a potential SPECT imaging agent for diazepam-intensive (DI) benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    He, Xiaoshu; Matecka, Dorota; Gu, Ziqiang; Rice, K C; Costa, B.R. de [National Inst. of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Lee, K S [National Inst. of Mental Health, Washington, DC (United States); Wong, Garry; Skolnick, Phil [National Inst. of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States). Lab. of Neuroscience

    1994-01-01

    [[sup 123]I]tert-Butyl 8-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine 3-carboxylate ([[sup 123]I]3), a high affinity and selective radioligand for the diazepam insensitive (DI) benzodiazepine receptor was synthesized in 2 steps from tert-butyl 8-bromo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiaz epine 3-carboxylate. (Author).

  11. Cloning and expression of the translocator protein (18 kDa), voltage-dependent anion channel, and diazepam binding inhibitor in the gonad of largemouth bass (Micropterus salmoides) across the reproductive cycle.

    Science.gov (United States)

    Doperalski, Nicholas J; Martyniuk, Christopher J; Prucha, Melinda S; Kroll, Kevin J; Denslow, Nancy D; Barber, David S

    2011-08-01

    Cholesterol transport across the mitochondrial membrane is rate-limiting for steroidogenesis in vertebrates. Previous studies in fish have characterized expression of the steroidogenic acute regulatory protein, however the function and regulation of other genes and proteins involved in piscine cholesterol transport have not been evaluated. In the current study, mRNA sequences of the 18 kDa translocator protein (tspo; formerly peripheral benzodiazepine receptor), voltage-dependent anion channel (vdac), and diazepam binding inhibitor (dbi; also acyl-CoA binding protein) were cloned from largemouth bass. Gonadal expression was examined across reproductive stages to determine if expression is correlated with changes in steroid levels and with indicators of reproductive maturation. In testis, transcript abundance of tspo and dbi increased with reproductive maturation (6- and 23-fold maximal increase, respectively) and expression of tspo and dbi was positively correlated with reproductive stage, gonadosomatic index (GSI), and circulating levels of testosterone. Testis vdac expression was positively correlated with reproductive stage and GSI. In females, gonadal tspo and vdac expression was negatively correlated with GSI and levels of plasma testosterone and 17β-estradiol. Ovarian dbi expression was not correlated with indicators of reproductive maturation. These studies represent the first investigation of the steroidogenic role of tspo, vdac, and dbi in fish. Findings suggest that cholesterol transport in largemouth bass testis, but not in ovary, may be transcriptionally-regulated, however further investigation will be necessary to fully elucidate the role of these genes in largemouth bass steroidogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Use of diazepam and ketamine anaesthesia in prevention of capture ...

    African Journals Online (AJOL)

    Capture or exertion myopathy (CM) is an attendant complication of manual restraint in ratites, asides physical injuries that handlers may suffer. CM arises from a combination of stress and anaerobic glycolysis during handling. This work was carried out to restrain and immobilize two ostriches (Struthio camelus) in a bid to ...

  13. Humid storage conditions increase the dissolution rate of diazepam from solid dispersions prepared by melt agglomeration

    DEFF Research Database (Denmark)

    Jørgensen, Anna Cecilia; Torstenson, Anette Seo

    2008-01-01

    The purpose of this study is to investigate the effect of cooling mode and storage conditions on the dissolution rate of a solid dispersion prepared by melt agglomeration. The aim has been to relate this effect to the solid state properties of the agglomerates. The cooling mode had an effect on t...

  14. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    DEFF Research Database (Denmark)

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    modulator of the GABAA receptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we....... There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by 1H nuclear magnetic resonance spectroscopy and the exon-intron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation...... sites and to examine if transcripts from the ACBP/DBI gene were subject to alternative processing. In both brain and liver, transcription is initiated from two major and multiple minor initiation sites. No evidence for alternative splicing was obtained. The promoter region of the ACBP/DBI gene...

  15. Episodic epileptic verbal auditory agnosia in Landau Kleffner syndrome treated with combination diazepam and corticosteroids.

    Science.gov (United States)

    Devinsky, Orrin; Goldberg, Rina; Miles, Daniel; Bojko, Aviva; Riviello, James

    2014-10-01

    We report 2 pediatric patients who presented initially with seizures followed by subacute language regression characterized by a verbal auditory agnosia. These previously normal children had no evidence of expressive aphasia during their symptomatic periods. Further, in both cases, auditory agnosia was associated with sleep-activated electroencephalographic (EEG) epileptiform activity, consistent with Landau-Kleffner syndrome. However, both cases are unique since the episodic auditory agnosia and sleep-activated EEG epileptiform activity rapidly responded to combination therapy with pulse benzodiazepine and corticosteroids. Further, in each case, recurrences were characterized by similar symptoms, EEG findings, and beneficial responses to the pulse benzodiazepine and corticosteroid therapy. These observations suggest that pulse combination high-dose corticosteroid and benzodiazepine therapy may be especially effective in Landau-Kleffner syndrome. © The Author(s) 2014.

  16. Reversion of methacholine induced bronchoconstriction with inhaled diazepam in patients with asthma

    OpenAIRE

    Miric, Mirjana; Ristic, Sinisa; Joksimovic, Bojan N; Medenica, Snezana; Racic, Maja; Ristic, Slavica; Joksimovic, Vedrana R; Skipina, Mirjana

    2016-01-01

    Background: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. Aim: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. Patients and Methods: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progr...

  17. Oxiracetam prevented the scopolamine but not the diazepam induced memory deficits in mice

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2002-01-01

    Roč. 133, č. 2 (2002), s. 395-399 ISSN 0166-4328 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : amnesia * oxiracetam * scopolamine Subject RIV: FH - Neurology Impact factor: 2.791, year: 2002

  18. EFFECTS OF DIAZEPAM ON THE BEHAVIORAL RESPONSE TO STRESS IN NULLIPAROUS AND PRIMIPAROUS RATS

    Directory of Open Access Journals (Sweden)

    C. F. R. Garcia

    2017-10-01

    Full Text Available Reproductive experience (RE, i.e. the conjunct of gestation, parturition and lactation, is associated with alterations in secretions of hormones, reducing, for example, steroids and prolactin, possibly for the rest of a female’s life. Responses to stress are related to a behavioral expression of anxiety in the elevated plus-maze, once stress has an anxiogenic effect in this experimental model; both responses, to stress and anxiety, can be permanently modified in function of the ER. Besides, reduction in seprimiparous females’ sensibility to stress has been demonstrated. In this way, the results obtained until the present moment suggests that stress models the behavioral responses to stress and consequently to reproductive experience and that the hormonal scenery related to the estral cycle phase participates in this modulation. In this way too, the reproductive experience is able to reduce the sensibility to stress; however this fact is also influenced by the estral cycle phase.

  19. Effect of breastfeeding piperine on the learning of offspring mice: interaction with caffeine and diazepam

    OpenAIRE

    Moghadamnia, Ali Akbar

    2010-01-01

    Ali Akbar Moghadamnia1,2, Vahid Zangoori2, Seyed Sadegh Zargar-Nattaj2, Pooya Tayebi2, Yasaman Moghadamnia3, Seyed Gholam Ali Jorsaraei41Cellular and Molecular Biology Research Center, Department of Pharmacology, 2Department of Pharmacology, 3Department of Physics, Alzzahra University, Babol University of Medical Sciences, Tehran, Iran; 4Department of Anatomical Iran; Sciences and Embryology, Tehran, IranAbstract: Piperine, the main alkaloid of black pepper (Piper nigrum), has been suggested ...

  20. Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature

    DEFF Research Database (Denmark)

    Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe

    2016-01-01

    with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug...

  1. The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure

    NARCIS (Netherlands)

    Broeders, Jessica J W; Hermens, Joop L M; Blaauboer, Bas J; Zurich, Marie-Gabrielle

    2015-01-01

    Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo

  2. "Diazepam loading": ¿Can a strategy for preventing alcohol withdrawal be used to treat benzodiazepine use disorder?

    Science.gov (United States)

    Oliveras, Clara; Fortea, Adriana; Espinosa, Laura; Barrio, Pablo; Lligoña, Anna; Balcells-Olivero, Mercè

    2018-04-15

    Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are widely used to treat insomnia and anxiety, despite having long-term adverse side effects. (Fortea González, Oriolo, Balcells Oliveró, Sánchez Del Valle & Castellvi, 2017). As with alcohol, continued use can lead to tolerance and dependence phenomena. Discontinuation in such cases can produce abstinence symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y Murnion, 2015).

  3. The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

    Science.gov (United States)

    2012-01-01

    progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

  4. Incorporation of radioactive labelled cholin and palmitate into lung lecithin of rabbits treated with high doses of bromcarbamides, barbiturates and diazepam

    International Nuclear Information System (INIS)

    Wichert, P. von; Schmidt, C.; Pomraenke, K.; Wiegers, U.

    1977-01-01

    Severe intoxications with bromcarbamides often show respiratory complications. To answer the question if there is a direct effect of the drug on lung tissue the incorporation of radioactive labelled choline and palmitate into lung lecithin was investigated. The phospholipid metabolism is in close relation to the surfactant system of the lung. Secondly the influence of bromcarbamides was compared with other hypnotic drugs. There was a reduction of palmitate incorporation into lung lecithin down to 40%, whereas the incorporation of choline increases in bromcarbamide intoxication. The relation between palmitate and choline incorporation was 6.77 in the controls and it decreases to 2-3 in the bromcarbamide group. The total phospholipid content in the lung/g wet weight remained unchanged in all experiments. From this data it is concluded, that these drugs cause a reduction of fatty acid exchange of the lecithin molecules of the lung. This might lead to the production of non surface active lecithin. The clinical and the morphological aspects of severe bromcarbamide intoxication are consistent with a perturbation of the surfactant function. (orig./MG) [de

  5. Comparison of Baseline Behavior and the Developmental Effects of Diazepam on Locomotor Activity in 3 Strains of Larval Zebrafish (Danio rerio)

    Science.gov (United States)

    Choice of strain is an important consideration in zebrafish husbandry and research. In the scientific literature there is concern that zebrafish strains may behave and respond differently to toxicants. A few studies have compared the baseline behavior of various strains of larv...

  6. Dgroup: DG02388 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG02388 Chemical ... DGroup Diazepam ... D00293 ... Diazepam (JP17/USP/INN) ... ATC code: ...N05BA01 Antianxiety, Minor tranquilizer, Sedative-hypnotic Benzodiazepine derivative GABRA/GABRB/GABRD/GABRE

  7. Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques.

    Science.gov (United States)

    van Drooge, D J; Hinrichs, W L J; Visser, M R; Frijlink, H W

    2006-03-09

    The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for diazepam. These observations indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP-diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated diazepam. TMDSC and DVS results were used to estimate the size of diazepam clusters in freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition the amount of molecularly dispersed

  8. Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques

    NARCIS (Netherlands)

    van Drooge, D J; Hinrichs, W L J; Visser, M R; Frijlink, H W

    2006-01-01

    The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T-g), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam

  9. Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions

    NARCIS (Netherlands)

    Van Drooge, D.J.; Hinrichs, W.L.J.; Frijlink, H.W.

    2004-01-01

    In this study, anomalous dissolution behaviour of tablets consisting of sugar glass dispersions was investigated. The poorly aqueous soluble diazepam was used as a lipophilic model drug. The release of diazepam and sugar carrier was determined to study the mechanisms governing dissolution behaviour.

  10. The effects of cyclodextrins on drug release from fatty suppository bases : II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was

  11. ORF Alignment: NT_037436 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available hila melanogaster] sp|P42281|ACBP_DROME ... Acyl-CoA-binding protein homolog (ACBP) (Diazepam ... ... ... binding inhibitor homolog) (DBI) gb|AAA21650.1| ... diazepam binding inhibitor gb|AAA21649.1| diazep

  12. Benzodiazepine effect of 125I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

    International Nuclear Information System (INIS)

    Fukumitsu, Nobuyoshi; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

    2005-01-01

    To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated 125 I-iomazenil ( 125 I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of 125 I-IMZ of the D (10) group were significantly lower (P 125 I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which 125 I-IMZ binding is strongly affected by administration of diazepam

  13. Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

    National Research Council Canada - National Science Library

    Shih, Tsung-Ming; Rowland, Tami C; McDonough, John H

    2007-01-01

    Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl...

  14. Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease

    DEFF Research Database (Denmark)

    Bahdoudi, Seyma; Ghouili, Ikram; Hmiden, Mansour

    2018-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which...

  15. NJP VOLUME 40 No 1B

    African Journals Online (AJOL)

    Prof Ezechukwu

    2012-05-26

    May 26, 2012 ... lus found in the soil and gastrointestinal tract of man and ... diazepam, adequate nutrition and ensuring primary im- ... peripheral nervous systems as a result of abnormal con- ... to micronutrient deficiency including calcium.

  16. Intraosseous (IO) route

    African Journals Online (AJOL)

    MBY

    Fluid, blood, antibiotics, glucose, diazepam, and furosemide were given successfully with resultant effect ... whom intra-vascular access failed and as an alternative. Introduction .... transfusion was carried out by conventional gravity with clinical ...

  17. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB

    1998-01-01

    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and

  18. Anaesthesia for Laryngoscopy and Microsurgery of the Larynx

    African Journals Online (AJOL)

    of Sanders' injector technique; using the Venturi principle to perform ... tained with intravenous agents and muscle relaxants as required. ... range of drugs including droperidol (Inapsin), diazepam. (Valium) ... Five or 6 sprays are delivered.

  19. Non-invasive and non-chemical method of stimulating the brain and ...

    African Journals Online (AJOL)

    Locomotor activity in normal rats, measured for 10 seconds, averaged 10.1±4.1 ... method of stimulating the CNS and increasing its levels of catecholamines. ... Keywords: Hypermotility, Noradrenergic pathway, Diazepam, GABA Receptors

  20. New generic approach to the treatment of organophosphate poisoning: Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    Helden, H.P.M. van; Groen, B.; Moor, E.; Westerink, B.H.C.; Bruijnzeel, P.L.B.

    1998-01-01

    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and

  1. Frequency, Levels and Predictors of Potential Drug-Drug ...

    African Journals Online (AJOL)

    major or moderate interactions included rifampin + pyrazinamide (14 cases), phenobarbital + diazepam (14), dexamethasone + rifampin (8), amikacin + furosemide (7), furosemide + captopril (7), dexamethasone + phenobarbital (6), phenobarbital + divalproex sodium (6), isoniazid + rifampin (5) amikacin + ibuprofen (5), ...

  2. Eclampsia and Pregnancy Outcome at Lautech Teaching Hospital ...

    African Journals Online (AJOL)

    policies supporting financial protection in times of ill health, non-implementation of .... Measure of association was carried out using Fisher's exact test and level of .... diazepam alone was used in management of eclampsia in the. Benin centre ...

  3. Interaction of rocuronium with human liver cytochromes P450

    OpenAIRE

    Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

    2015-01-01

    Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver micro...

  4. Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells.

    OpenAIRE

    Matthew, E; Laskin, J D; Zimmerman, E A; Weinstein, I B; Hsu, K C; Engelhardt, D L

    1981-01-01

    We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein-labeled protein. Our studies also showed tha...

  5. Paradoxical therapy in conversion disorder

    OpenAIRE

    ATAOĞLU, Ahmet

    1998-01-01

    Paradoxical therapy consists of suggesting that the patient intentionally engages in the unwanted behaviour, such as performing complusive ritual or bringing on a conversion attack. In this study paradoxical intention (PI) was used with to half of the patients with conversion disorders, while the other half were treated with diazepam in order to examine the efficiency of the PI versus diazepam in conversion disorder. Patients treated with PI appeared to have a greater improvement r...

  6. Neuro-pharmacological functional MRI of epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji [Okayama Univ. (Japan). School of Medicine; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-03-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

  7. Innovative Approach for Interstitial Cystitis: Vaginal Pessaries Loaded Diazepam—A Preliminary Study

    Directory of Open Access Journals (Sweden)

    P. Capra

    2013-01-01

    Full Text Available Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta-glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated.

  8. Benzodiazepine effect of {sup 125}I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumitsu, Nobuyoshi [Proton Medical Research Center, University of Tsukuba, Ibaragi, 305-8575 (Japan)]. E-mail: gzl13162@nifty.ne.jp; Ogi, Shigeyuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Uchiyama, Mayuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Mori, Yutaka [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan)

    2005-01-01

    To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated {sup 125}I-iomazenil ({sup 125}I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of {sup 125}I-IMZ of the D (10) group were significantly lower (P<.05) than those of the D (0) group in the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus. The serum corticosterone level ratio in the D (10) group was significantly lower than that in the D (0) group (P<.05). From the change in serum corticosterone levels, diazepam attenuated the psychological stress produced by the physical stress to animals in adjacent compartments. From the reduced binding of {sup 125}I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which {sup 125}I-IMZ binding is strongly affected by administration of diazepam.

  9. Neuro-pharmacological functional MRI of epilepsy

    International Nuclear Information System (INIS)

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-01-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

  10. Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

    2016-01-01

    Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

  11. Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Capacio, B.R.; Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Gales, V.

    1992-12-31

    The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.

  12. Interaction of rocuronium with human liver cytochromes P450.

    Science.gov (United States)

    Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

    2015-02-01

    Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  13. Modified Suanzaorentang Had the Treatment Effect for Generalized Anxiety Disorder for the First 4 Weeks of Paroxetine Medication: A Pragmatic Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Ming-Fen Song

    2017-01-01

    Full Text Available Background. Paroxetine does not show satisfactory therapeutic effect for generalized anxiety disorder (GAD patients for the first 2–4 weeks of medication. Diazepam is always concurrently used although it has some shortcomings such as physical dependence and withdrawal reactions. In this study, we aimed to identify whether modified Suanzaorentang (MSZRT, a combined Chinese formula including Suanzaorentang (SZRT and Zhizichitang (ZZCT, could control the anxiety of GAD for the first 4 weeks of paroxetine medication. Methods. 156 GAD patients were randomized to the treatment of paroxetine, paroxetine-diazepam, or paroxetine-MSZRT for 4 weeks. Hamilton Anxiety Scale (HAMA Test and Self-Rating Anxiety Scale (SAS Test were determined each week as the evaluation of clinical efficacy. Adverse events (AEs were also closely observed by performing the Treatment Emergent Symptom Scale (TESS Test. Results. Both paroxetine-MSZRT and paroxetine-diazepam decreased more HAMA and SAS total scores than paroxetine from weeks 1 to 3. Paroxetine-MSZRT as well as paroxetine-diazepam had an obviously higher onset rate than paroxetine in each week. After 4 weeks’ treatment, the overall effectiveness rate in the paroxetine-MSZRT group (90.00% was obviously higher than those of the paroxetine group (74.42% but did not significantly differ from the paroxetine-diazepam group (93.88%. Conclusion. MSZRT had the treatment effect for GAD when paroxetine was used for the first 4 weeks.

  14. Synthesis, Anticonvulsant, Sedative and Anxiolytic Activities of Novel Annulated Pyrrolo[1,4]benzodiazepines

    Directory of Open Access Journals (Sweden)

    Kumaraswamy Sorra

    2014-09-01

    Full Text Available Four new pentacyclic benzodiazepine derivatives (PBDTs 13–16 were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.

  15. Psychology and pediatric dentistry: the contribution of behaviour functional analysis / Psicologia e odontopediatria: a contribuição da análise funcional do comportamento

    Directory of Open Access Journals (Sweden)

    Antonio Bento Alves de Moraes

    2004-01-01

    Full Text Available The aim of this study was to carry out a functional description of the pediatric dentists' behavior concerning professional performance. Subjects were 3 uncooperative dental patients who were treated using placebo or diazepam. Dental sessions were videotaped. Procedures and behaviors were recorded in 15-second intervals. Results revealed that children's level of cooperative behavior may be a considered variable that affect professional behaviors. Diazepam was not effective. "Guidance" was predominantly used by the dentist and evoked cooperative behavior with two patients. The results express the contribution of behaviour functional analysis to the study of patterns of interaction between the dental practitioner and child patient.

  16. Chemical and biological studies of Lobelia flaccida (C. Presl) A.DC ...

    African Journals Online (AJOL)

    Chemical and biological studies of Lobelia flaccida (C. Presl) A.DC leaf: a medicinal plant used by traditional healers in Eastern Cape, South Africa. ... (85 mg/kg, intraperitoneally)-induced convulsion model in mice, normal saline and diazepam (1 mg/kg, i.p.) served as negative and positive control groups respectively.

  17. Anaestesia for high dose-rate after-loading treatment for carcinoma of the uterus. Chapter 5

    International Nuclear Information System (INIS)

    Moore, M.R.

    1980-01-01

    Details of the method of anaesthesia used in patients receiving regular Cathetron treatment for carcinoma of the cervix are given. The drugs used for premedication are prochlorperazine, pethidine and atropine and for induction are prochlorperazine, diazepam, phenoperidine and thiopentone. The advantages of using these particular drugs compared to others generally used are discussed. (U.K.)

  18. Effect of anesthetics on the radiosensitivity of a murine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sheldon, P.W.; Chu, A.M.

    1979-09-01

    The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken to minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam.

  19. Maternal and perinatal outcome of patients with severe pre ...

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Eclampsia occurred in 3 members of the diazepam group and none in the MgSO group. There were no .... in pre-eclampsia- abnormal trophoblastic invasion of uterine blood vessels and endothelial cell ..... O'Brien E, Conroy R & Darling MR.

  20. Enhancement of Aqueous Solubility and Oral Bioavailability of ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research August 2015; 14 (8): 1333- ... 1Department of Pharmaceutics, 2Department of Pharmaceutical Quality ... of its water solubility and pharmacokinetic profile. EXPERIMENTAL. Materials ... Diazepam was procured from INTAS Lab Pvt ... 1.2, 4.5, 6.8 and 7.4) and distilled water were.

  1. Febrile seizures

    Science.gov (United States)

    ... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

  2. Download this PDF file

    African Journals Online (AJOL)

    Administrator

    Methods: A hundred and twenty consecutive admissions with eclampsia managed in ... Case fatality rate was 11.7%, diazepam use failed to achieve significant association ... PMB 3452, Zaria road ... management of preeclampsia. ... diagnosis of cerebral malaria and other medical ..... factors for cerebral palsy in term infants.

  3. 78 FR 62676 - Anthony E. Wicks, M.D. Decision and Order

    Science.gov (United States)

    2013-10-22

    ... registration BW7987184, while listing his address as Pain Management of Winter Springs, 165 W. SR 434, Winter... practice address. Id. at 2, ] 5. \\2\\ Documentary evidence, which the Government acquired through... prescriptions for oxycodone,\\4\\ diazepam, and lorazepam.\\5\\ GX 15, at 2, ] 7; GX 13. \\3\\ The documentary...

  4. Some behavioural studies on methanol root bark extract of Burkea ...

    African Journals Online (AJOL)

    The research was conducted to evaluate some central nervous system properties of the root bark methanol extractof B. africana in mice. It involved the following animal models: diazepam-induced sleep, hole-board and walking beam assay. Results: The methanol extract showed a significant decrease in the onset of sleep ...

  5. Journal of Special Operations Medicine, Volume 6, Edition 4

    Science.gov (United States)

    2006-01-01

    Gay Thompson worked on the First Edition as the Managing Editor and will be doing the same this time. Dr. Les Fenton , who recently retired from... cosmetic surgery: Low dosage ketamine-diazepam anesthesia. Laryngoscope 1978;88: 1709-12. 52. Tucker MR, Hann JR, Phillips CL, et al. Subanesthetic

  6. A KCNQ channel opener for experimental neonatal seizures and status epilepticus

    Science.gov (United States)

    Raol, YogendraSinh H.; Lapides, David A.; Keating, Jeffery; Brooks-Kayal, Amy R.; Cooper, Edward C.

    2009-01-01

    Objective Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. Methods We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. Results Unlike phenobarbital or diazepam, flupirtine prevented animals from developing status epilepticus (SE) when administered prior to kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced SE. Flupirtine caused dose-related sedation and suppressed EEG activity, but did not result in respiratory suppression or result in any mortality. Interpretation Flupirtine appears more effective than either of two commonly used anti-epileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children. PMID:19334075

  7. Manual control analysis of drug effects on driving performance

    Science.gov (United States)

    Smiley, A.; Ziedman, K.; Moskowitz, H.

    1981-01-01

    The effects of secobarbital, diazepam, alcohol, and marihuana on car-driver transfer functions obtained using a driving simulator were studied. The first three substances, all CNS depressants, reduced gain, crossover frequency, and coherence which resulted in poorer tracking performance. Marihuana also impaired tracking performance but the only effect on the transfer function parameters was to reduce coherence.

  8. Enhancement of GABAergic transmission by zolpidem, an imidazopyridine with preferential affinity for type I benzodiazepine receptors.

    Science.gov (United States)

    Biggio, G; Concas, A; Corda, M G; Serra, M

    1989-02-28

    The effect of zolpidem, an imidazopyridine derivative with high affinity at the type I benzodiazepine recognition site, on the function of the GABAA/ionophore receptor complex was studied in vitro. Zolpidem, mimicking the action of diazepam, increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced [35S]TBPS binding in rat cortical membrane preparations. Zolpidem was less effective than diazepam on the above parameters. Zolpidem induced a lower increase of [3H]GABA binding (23 vs. 35%) and muscimol-stimulated 36Cl- uptake (22 vs. 40%) and a smaller decrease of [35S]TBPS binding (47 vs. 77%) than diazepam. The finding that zolpidem enhanced the function of GABAergic synapses with an efficacy qualitatively and quantitatively different from that of diazepam suggests that this compound is a partial agonist at the benzodiazepine recognition site. Thus, our results are consistent with the view that the biochemical and pharmacological profile of a benzodiazepine recognition site ligand reflects its efficacy to enhance GABAergic transmission. Whether the preferential affinity of zolpidem at the type I site is involved in its atypical biochemical and pharmacological profile remains to be clarified.

  9. PATTERNS OF SEVEN AND COMPLICATED MALARIA IN CHILDREN

    African Journals Online (AJOL)

    GB

    found registered in the delivery logbook, their card number documented in the delivery logbook was used as an initial entry to access their chart (where the detailed ..... Eclampsia Trial. Lancet, 1995; 345: 1455–63. 25. Duley L, Henderson-Smart DJ, Walker GJ,. Chou D. Magnesium sulphate versus diazepam for eclampsia.

  10. Variables determining the success of ultrasound-guided hydrostatic ...

    African Journals Online (AJOL)

    Department of Pediatric Surgery, Faculty of Medicine, Tanta University Hospitals,. Tanta, Egypt ... Ultrasound was performed using warm normal saline 0.9% through a Foley's catheter that was passed into the rectum. Irritable infants received slow intrave- nous diazepam ... duplication cyst) and resection (13.6%) Table 4.

  11. Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

    NARCIS (Netherlands)

    Srinarong, Parinda; Kouwen, Sander; Visser, Marinella R; Hinrichs, Wouter L J; Frijlink, Henderik W

    2010-01-01

    The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides

  12. Incorporation of lipophilic drugs in sugar glasses by lyophilization using a mixture of water and tertiary butyl alcohol as solvent

    NARCIS (Netherlands)

    Van Drooge, D.J.; Hinrichs, W.L.J.; Frijlink, H.W.

    2004-01-01

    In this study, anew and robust method was evaluated to prepare physically stable solid dispersions. Trehalose, sucrose, and two inulins having different chain lengths were used as carrier. Diazepam, nifedipine, Delta(9)-tetrahydrocannabinol, and cyclosporine A were used as model drugs. The sugar was

  13. [Epileptic seizures during childbirth in a patient with idiopathic generalised epilepsy

    NARCIS (Netherlands)

    Voermans, N.C.; Zwarts, M.J.; Renier, W.O.; Bloem, B.R.

    2005-01-01

    During her first pregnancy, a 37-year-old woman with idiopathic generalised epilepsy that was adequately controlled with lamotrigine experienced a series of epileptic seizures following an elective caesarean section. The attacks were terminated with diazepam. The following day, she developed

  14. PREPARATION, CHARACTERIZATION, AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRIN .3. DRUG-RELEASE FROM FATTY SUPPOSITORY BASES CONTAINING AMYLODEXTRIN

    NARCIS (Netherlands)

    TEWIERIK, GHP; EISSENS, AC; LERK, CF

    Drug release from fatty suppository bases containing a solid dispersion of diazepam with amylodextrin or a complex of prednisolone with amylodextrin was analyzed in a flow-through model. Being present as a suspension in the fatty base, particles of complex or solid dispersion are transported to the

  15. The effects of cyclodextrins on drug release from fatty suppository bases : III. Application of cyclodextrin derivatives

    NARCIS (Netherlands)

    Frijlink, H.W.; Paiotti, S.; Eissens, Anko; Lerk, C.F.

    1992-01-01

    The complexation of both n-butyl-4-aminobenzoate and diazepam with dimethyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, respectively, was studied. Solid complexes were prepared by freeze-drying. The complexes were incorporated in fatty suppositories and drug release was studied, both in

  16. Interaction of indomethacin with adult human albumin and neonatal serum

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R; Robertson, A

    1983-01-01

    The binding of indomethacin to albumin was investigated at 37 degrees C, pH 7.4. The first stoichiometric binding constant is 2.5 X 10(5) M-1. Indomethacin utilizes both the bilirubin and diazepam binding functions equally. The effect on bilirubin binding to albumin is negligible at therapeutic...

  17. Preliminary studies on the behavioural effects of the methanol ...

    African Journals Online (AJOL)

    The behavioural tests employed were diazepam-induced sleep onset and duration, hole board assay for exploratory activity, mouse beam walk assay for motor coordination, and the staircase test for the detection of anxiolytic compounds. Preliminary phytochemical screening was also carried out on the extract. Results: The ...

  18. Sedative properties of Mitracarpus villosus leaves in mice

    African Journals Online (AJOL)

    admin

    anxiolytics increase the head-dip counts. The reduction in the number of head dips shown by the extract is therefore an indication of the presence of psychoactive constituents that are sedative in nature. The sedative property of the plant was confirmed by its ability to potentiate the duration of diazepam induced sleep.

  19. Complications et prise en charge de la prééclampsie sévère et de l ...

    African Journals Online (AJOL)

    Results Overall, 158 patients were included with the mean age of 31.4±5,4 years. The most observed complications were acute renal failure (13.2%), HELLP syndrome (12.6%), infection (8.2%), placenta abruptio (3.8%) and acute pulmonary edema (3.8%). Delivery was mainly by caesarean section (57.8%). Diazepam was ...

  20. Effect of anesthetics on the radiosensitivity of a murine tumor

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Chu, A.M.

    1979-01-01

    The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken to minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam

  1. ANXIOLYTIC ACTIVITY OF OCIMUM SANCTUM LEAF EXTRACT

    OpenAIRE

    Chattopadhyay, R.R.

    1994-01-01

    The anxiolytic activity of Ocimum sanctum leaf extract was studied in mice. O.sanctum leaf extract produced significant anxiolytic activity in plus – maze and open field behaviour test models. The effect was compared with diazepam, a standard antianxiety drug.

  2. Behavioural Effects of Methanol Stem Bark Extract of Boswellia

    African Journals Online (AJOL)

    Dr Olaleye

    respectively and observed for signs of toxicity and death within. 24 hours. The LD50 was determined by calculating the geometric mean of the lowest dose that caused death and the highest dose for which the animal survived. Behavioural studies. Diazepam-induced sleep test in mice: The method described by Rakotonirina ...

  3. Animal Research International

    African Journals Online (AJOL)

    Evaluation of the use of pentazocine in combination with diazepam and ketamine for surgical anaesthesia in rabbits · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Rita Ijeoma Udegbunam, Sunday Ositadimma Udegbunam, Austine Chukwudum Onuba, Nnenna Ebere Ugwu ...

  4. Drug: D00293 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00293 Drug Diazepam (JP17/USP/INN); Diastat (TN); Valium (TN) ... C16H13ClN2O D00293....gif ... Neuropsychiatric agent ... DG01567 ... GABA-A receptor agonist ... DG01914 ... Anxiolytics, benzodiazepine deriv...ory: 1124 ATC code: N05BA01 Chemical group: DG02388 ... Benzodiazepine derivative G

  5. Drug: D00370 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01633 ... CYP3A substrate Same as: C07125 ATC code: N05CD07 ... Temazepam is metabolite of Diazepam. Benzodiaz...ychiatric agent ... DG01835 ... Benzodiazepine sedative-hypnotics ... DG01567 ... GABA-A receptor agonist Cyp substrate

  6. Tricyclic Antidepressants Found in Pilots Fatally Injured in Civil Aviation Accidents

    Science.gov (United States)

    2014-11-01

    chlordiazepoxide, diazepam/nordiazepam, oxazepam, and temazepam), beta - blockers (atenolol and propranolol), calcium-channel blockers (verapamil/norverapamil...Drug therapy of depression and anxiety disorders. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s the pharmacological basis of

  7. Super Refractory Status Epilepticus: A Case Report from Livingstone ...

    African Journals Online (AJOL)

    Case History: A 22 years old male nursing student with first episode of generalized tonic clonic seizures brought into the medical emergency of Livingstone Central Hospital. He was treated with 60mg of diazepam but fits continued and patient was transferred to ICU, where he was treated with phenobarbitone infusion with ...

  8. Hypertonia

    Science.gov (United States)

    ... and in a variety of directions. View Full Definition Treatment Muscle relaxing drugs such as baclofen, diazepam, and dantrolene may be ... exercising within their limits and using physical therapy. Drugs that affect the dopamine system ... Definition Hypertonia is a condition in which there is ...

  9. PREPARATION, CHARACTERIZATION AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRINS .4. DRUG-RELEASE FROM CAPSULES AND TABLETS CONTAINING AMYLODEXTRIN

    NARCIS (Netherlands)

    WIERIK, GHPT; EISSENS, AC; LERK, CF

    1993-01-01

    Linear dextrin (amylodextrin) and its soluble fraction were investigated for their suitability to enhance diazepam release from capsules and tablets. Drug release was analyzed in the USP XXI paddle apparatus and performed in phosphate buffer pH 6.8, with and without alpha-amylase, and in 0.1 N HCl

  10. Comparison of three Ketamine drug combinations for short term ...

    African Journals Online (AJOL)

    Ketamine (XK) at a dose of 0.05/25mg/kg, acepromazine/ketamine (AK) at a dose of 0.05/25mg/kg and diazepam/ketamine (DK) at a dose of 0.5/25mg/kg were evaluated and compared in five non-fasted West African Dwarf (WAD) goats. The mean ...

  11. Degradation of benzodiazepines after 120 days of EMS deployment.

    Science.gov (United States)

    McMullan, Jason T; Jones, Elizabeth; Barnhart, Bruce; Denninghoff, Kurt; Spaite, Daniel; Zaleski, Erin; Silbergleit, Robert

    2014-01-01

    EMS treatment of status epilepticus improves outcomes, but the benzodiazepine best suited for EMS use is unclear, given potential high environmental temperature exposures. To describe the degradation of diazepam, lorazepam, and midazolam as a function of temperature exposure and time over 120 days of storage on active EMS units. Study boxes containing vials of diazepam, lorazepam, and midazolam were distributed to 4 active EMS units in each of 2 EMS systems in the southwestern United States during May-August 2011. The boxes logged temperature every minute and were stored in EMS units per local agency policy. Two vials of each drug were removed from each box at 30-day intervals and underwent high-performance liquid chromatography to determine drug concentration. Concentration was analyzed as mean (and 95%CI) percent of initial labeled concentration as a function of time and mean kinetic temperature (MKT). 192 samples were collected (2 samples of each drug from each of 4 units per city at 4 time-points). After 120 days, the mean relative concentration (95%CI) of diazepam was 97.0% (95.7-98.2%) and of midazolam was 99.0% (97.7-100.2%). Lorazepam experienced modest degradation by 60 days (95.6% [91.6-99.5%]) and substantial degradation at 90 days (90.3% [85.2-95.4%]) and 120 days (86.5% [80.7-92.3%]). Mean MKT was 31.6°C (95%CI 27.1-36.1). Increasing MKT was associated with greater degradation of lorazepam, but not midazolam or diazepam. Midazolam and diazepam experienced minimal degradation throughout 120 days of EMS deployment in high-heat environments. Lorazepam experienced significant degradation over 120 days and appeared especially sensitive to higher MKT exposure.

  12. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  13. Development of a laboratory model to assess fear and anxiety in cats.

    Science.gov (United States)

    de Rivera, Christina; Ley, Jacqui; Milgram, Bill; Landsberg, Gary

    2017-06-01

    Objectives The objectives of this study were: (1) to develop a laboratory-based model to assess fear and anxiety in cats using the feline open-field test (OFT) and the feline human interaction test (HIT); and (2) to validate the model using diazepam, a known anxiolytic. Methods Laboratory-housed cats (n = 41) were first classified as fearful, mildly fearful or non-fearful by a technician familiar with the cats and also by veterinary behaviorists (GL, JL), by assessing the cats' behavior in their home rooms. In experiment 1, each cat's behavior was assessed in an OFT and an HIT. In experiment 2, after administration of the anxiolytic diazepam, a subset of the cats was re-tested. Results In experiment 1, the OFT revealed significant group effects on two measures: duration of inactivity, and vocalization. Fearful animals had significantly longer periods of inactivity than non-fearful animals. Non-fearful and mildly fearful cats vocalized more frequently than fearful cats. In the HIT, fearful cats travelled less than non-fearful and mildly fearful cats. Fearful and mildly fearful animals had significantly longer durations of inactivity, and non-fearful and mildly fearful cats had a significantly higher frequency of vocalization compared with fearful cats. In experiment 2, in the OFT, treatment with diazepam caused an increase in distance travelled, shorter durations of inactivity, and more frequent inactivity and vocalization. In the HIT, diazepam increased distance travelled and decreased duration of inactivity. Fearful cats spent significantly less time near the human compared with non-fearful cats, and this persisted under diazepam. Conclusions and relevance The feline OFT and feline HIT can be used jointly to assess the effects of medications or other therapies on fear and anxiety in the domestic cat.

  14. Comparative antistress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats

    Directory of Open Access Journals (Sweden)

    Manish Pal Singh

    2016-07-01

    Full Text Available Introduction: The human society has become complex. However, our physiological responses designed to cope with the ever-increasing adverse situations have not evolved appreciably during the past thousand years. The failure of successful adaptation during stressful situations has resulted in stress-related illnesses. Methods: The objective of the present study was to carry out a comparative assessment of anti-stress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats. Long-term exposure to multiple stressors can cause depression. The unpredictable chronic administration of various mild stresses, a procedure known as “unpredictable chronic mild stress”, is one of the best-validated rodent models to study stress in animals, for its good etiological and predictive validity. Result: Diazepam, Withania somnifera, Vitis vinifera administration dose dependently reversed the increase in immobility period in stressed rats. In the study of locomotion activity of rats in elevated plus maze apparatus, Stress treated control group rats showed less no of entries in open arm and also less time spent in open arm. Vitis vinifera treated (p<0.0001, Withania somnifera treated (p<0.0001 and Diazepam treated group showed (p<0.0001 no. of entries in open arms which were more than control group and stressed groups. Stressed group produce less average time spent in open arm as compared to treatment groups as Withania somnifera (p<0.05, Vitis vinifera and diazepam. Withania somnifera group showed significant antistress locomotry behaviour in rats. Administration of Vitis vinifera, Withania somnifera and diazepam during stress period restored the ambulatory behaviour of the rats which can be correlated with restoration of plasma corticosterone level. Finally, the results of the present study justified that Withania somnifera, Vitis vinifera and diazepam exhibited significant antistress activity in rats.

  15. Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis.

    Science.gov (United States)

    Sánchez Fernández, Iván; Gaínza-Lein, Marina; Loddenkemper, Tobias

    2017-08-01

    To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: -$3.8/SS), intramuscular midazolam (ICER: -$64/SS), and rectal diazepam (ICER: -$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue

  16. Studies of the biotransformation and pharmacology of ketamine and its metabolites

    International Nuclear Information System (INIS)

    Leung, Y.

    1986-01-01

    The first part of the research is concerned with the synthesis, resolution and metabolism of norketamine, the primary metabolite of ketamine. Incubations of racemic norketamine, individual enantiomers of norketamine and the pseudoracemates in rat liver microsomes revealed stereoselectivity and enantiomeric interactions during the metabolism of norketamine. The second part of the research describes the synthesis of 6-OH-norketamine, the major secondary metabolite of ketamine, and reports on its pharmacological activity and cerebral distribution in the rat. Primary deuterium isotope effects associated with the metabolism and pharmacological activity of ketamine-N-CD 3 were examined in the third part of this research. The last part of the research deals with the effect of diazepam on the metabolic transformation of ketamine to norketamine in the rat. The fractions of ketamine metabolized to norketamine were found not to be different in the presence or the absence of diazepam

  17. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    International Nuclear Information System (INIS)

    Lummis, S.C.R.; Johnston, G.A.R.; Nicoletti, G.; Holan, G.

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial [ 3 H]diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli [ 3 H]diazepam binding are those that are active in displacing [ 3 H]benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed

  18. Pre-medication to block [{sup 18}F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients

    Energy Technology Data Exchange (ETDEWEB)

    Gelfand, Michael J.; O' Hara, Sara M.; Curtwright, Lois A.; MacLean, Joseph R. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2005-10-01

    Radiopharmaceutical uptake of [{sup 18}F]2-deoxy-2-glucose (FDG) in brown adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in children and adolescents. To determine whether [{sup 18}F]FDG uptake in brown adipose tissue can be adequately blocked by pre-medication other than moderate-dose oral diazepam. One hundred and eighteen [{sup 18}F]FDG PET body imaging studies were performed in 69 pediatric patients with a variety of solid tumors. The mean age at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were performed in patients younger than 10 years old. Seventy-six were performed in boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre-medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0 {mu}g/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate-dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of whom were known to have received opiates for pain during the 12 h before the study. Six body regions in the neck and chest were reviewed for [{sup 18}F]FDG uptake in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense uptake. Visual grades 2 and 3 were considered to interfere potentially with image interpretation in the neck and chest. Data were analyzed by multivariate regression using a Poisson distribution. [{sup 18}F]FDG uptake in brown adipose tissue was most often seen in the lateral neck region and superior and lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen near the costovertebral junctions (15 studies), in the superior and central neck in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake was thought to interfere potentially with image interpretation (visual grades 2 and 3) in 19 studies - in 6 of 23 (26.1%) studies after no pre-medication and no

  19. Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.

    Directory of Open Access Journals (Sweden)

    Rajput Muhammad Ali

    2013-01-01

    Full Text Available This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L. as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L., using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle, standard (diazepam and test (Trachyspermum ammi (L. extract. Trachyspermum ammi (L. demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L. and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L. showed antiepileptic activity, which may be due to the presence of thymol.

  20. Involvement of opioid and other systems in ethanol abstinence audiogenic seizures in the rat?

    Science.gov (United States)

    Kotlińska, J; Langwiński, R

    1985-01-01

    The action of opiate receptor agonists: (D-Ala2)-methionine enkephalinamide (D-MEA), morphine, heroin, etorphine, and antagonists: naloxone and diprenorphine on audiogenic seizures was tested during ethanol abstinence. The action of diazepam and clonidine was also tested Morphine (5 and 20 mg/kg), but not heroin and etorphine, given intraperitoneally inhibited the seizures, similarly as intraventricularly administered D-MEA did. However, morphine given by this route was ineffective. Diazepam and clonidine inhibited audiogenic seizures: the action of clonidine was counteracted by yohimbine, but not by prazosin. The results may be considered as supporting the hypothesis on the participation of opioid system in ethanol abstinence. However, the participation of gabergic and noradrenergic systems cannot be ruled out: these systems may possibly interact with the opioid system in evoking the symptoms of ethanol abstinence.

  1. Pre-medication to block [18F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients

    International Nuclear Information System (INIS)

    Gelfand, Michael J.; O'Hara, Sara M.; Curtwright, Lois A.; MacLean, Joseph R.

    2005-01-01

    Radiopharmaceutical uptake of [ 18 F]2-deoxy-2-glucose (FDG) in brown adipose tissue is noted on 15-20% of positron emission tomography (PET) scans in children and adolescents. To determine whether [ 18 F]FDG uptake in brown adipose tissue can be adequately blocked by pre-medication other than moderate-dose oral diazepam. One hundred and eighteen [ 18 F]FDG PET body imaging studies were performed in 69 pediatric patients with a variety of solid tumors. The mean age at the time of imaging was 12.9 years (range 1.2-22.6 years), and 33 studies were performed in patients younger than 10 years old. Seventy-six were performed in boys and 42 in girls. Patients were imaged using a dedicated PET camera. Pre-medication was given in 88 studies: 45 received intravenous fentanyl (0.75-1.0 μg/kg), 34 received low-dose oral diazepam (0.06 mg/kg) and 9 received moderate-dose oral diazepam (0.10 mg/kg). Thirty patients received no pre-medication, 7 of whom were known to have received opiates for pain during the 12 h before the study. Six body regions in the neck and chest were reviewed for [ 18 F]FDG uptake in brown adipose tissue. Uptake of FDG in brown fat was visually graded: 0 for no FDG uptake, 1 for low-grade uptake, 2 for moderate uptake, and 3 for intense uptake. Visual grades 2 and 3 were considered to interfere potentially with image interpretation in the neck and chest. Data were analyzed by multivariate regression using a Poisson distribution. [ 18 F]FDG uptake in brown adipose tissue was most often seen in the lateral neck region and superior and lateral to the lungs (in 36 and 39 studies, respectively). Uptake was also seen near the costovertebral junctions (15 studies), in the superior and central neck in 7 studies and in the anterior mediastinum in 2. Brown adipose tissue uptake was thought to interfere potentially with image interpretation (visual grades 2 and 3) in 19 studies - in 6 of 23 (26.1%) studies after no pre-medication and no opiates for pain, in 10 of

  2. Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs

    International Nuclear Information System (INIS)

    Bender, A.S.; Hertz, L.

    1988-01-01

    The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit [ 3 H]diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel

  3. Drug Facilitated Sexual Assault and That the Problems in Turkey

    Directory of Open Access Journals (Sweden)

    Nabi Kantarcı

    2012-10-01

    Full Text Available The assailants of sexuel assault to serve this purpose to the victims of many different drug can use. These drugs can be applied together with alcohol, soft drinks, water and other drinks can be given together. Most of these drugs tasteless and odorless. In a few minutes after ingestion chemical effect of drugs can start. Victims the conscious reduction and limitation of the physical move occur. Drug drinking from the pass the time until impact memory loss can occur. For this purpose the main benzodiazepines (Diazepam, flunitrazepam, lorazepam, etc., hypnotics (Zopiclone, zolpidem, anesthetics (Gama-hydroxybutyrate, ketamine, amphetamines (Metylendioxymetamphetamine=ecstasy, opiats (Cocaine, cannabis=marihuana and alcohols such as ethanol substances used. However in study frequently encountered in the literature; cocaine, cannabis, metylendioxymetamphetamine, zolpidem, ketamine hydrochloride, zopiclone, gamma hydroxybutirate, diazepam, flunitrazepam and the effects of these substances after oral ingestion were evaluated and the approach to victims.

  4. [Application possibilities of dynamic laser light scattering photometry for the examination of poly(ethylene glycol) suppositories].

    Science.gov (United States)

    Bácskay, I; Kéki, S; Deák, G; Zsuga, M; Mezey, G

    2001-08-01

    Status epilepticus is one of the most common neurologic emergencies in children, adolescents, and young adults. The advantage of diazepam suppository in medicinal therapy appears mainly in treatment of childhood epilepsy. A hydrophilic suppository base was investigated in solution by dynamic light scattering and results were compared to those of the membrane diffusion experiments measuring diazepam solubilization. According to the dynamic laser light scattering photometric measurements, the good solubilization effect of the macrogol mixture (5% Polysorbatum 20, 10% Macrogolum 400, 85% Macrogolum 1540) is explained by the formation of small, tight micellas. As the Polysorbatum 20 tenside resulted in the significant decrease (p < 0.05) of the formation of great micellas, its use led to the formation of small, tight, almost monodisperse micellas of 40-50 nm in the aqueous solution of the macrogol mixture.

  5. Rectal benzodiazepines for premedication in children. Review and personal experience.

    Science.gov (United States)

    Govaerts, M J; Capouet, V

    1987-01-01

    Modern anesthetic techniques have modified the aims of premedication in pediatric practice. Anxiolysis, amnesia and easiness of induction are now the the main targets. This paper reviews both the literature and the personal experience of the authors on the subject. Many authors now prefer a benzodiazepine. Rectal instillation of benzodiazepine in solution avoids the trauma of the intramuscular route and produces a faster and more predictable effect, than suppositories. Diazepam (.1 to .2 mg/kg) and flunitrazepam (40 to 80 micrograms/kg) have been extensively used in this indication. Diazepam's duration of elimination being much longer than that of flunitrazepam, this last drug is preferred by many pediatric anesthetists. Midazolam (.4 to .5 mg/kg) has a much faster onset and shorter duration of action. It should thus be preferred if the environment enables the administration of premedication within 10 to 15 minutes of induction.

  6. Excretory urography by subcutaneous injection of iodixanol in Persian squirrel (Sciurus anomalous)

    International Nuclear Information System (INIS)

    Veshkini, A.; Tavana, M.; Haghdost, I.S.; Masouleh, M.N.; Savojbolaghi, S.H.

    2011-01-01

    There are many indications for excretory urography in humans and animals. Intravenous urography (IVU) is the most practical method about other urography techniques are used because of difficulties for finding veins in IVU, due to small size of the patients. This study was performed to evaluate the feasibility of subcutaneous injection of iodixanol in providing a safe and diagnostic urogram in Persian squirrel. Twelve clinically healthy adult Persian squirrels were prepared and kept for two weeks prior to study. Blood tests were performed 7 days prior to the study. After eighteen hour fasting, animals were sedated by using xylazine/diazepam cocktail (xylazine 5mg/kg, diazepam 30mg/kg). Lateral and ventrodorsal control radiographs were taken. Thirteen hundred and 1800 mg iodine per kilogram body weight of iodixanol was injected subcutaneously over shoulder area in Persian squirrels (each dose for six Persian squirrels). Lateral and ventrodorsal radiographs were taken every 5 m

  7. GABA-B receptor activation and conflict behavior

    International Nuclear Information System (INIS)

    Ketelaars, C.E.J.; Bollen, E.L.; Rigter, H.; Bruinvels, J.

    1988-01-01

    Baclofen and oxazepam enhance extinction of conflict behavior in the Geller-Seifter test while baclofen and diazepam release punished behavior in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA-A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [ 3 H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increase Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behavior and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex. 50 references, 1 figure, 4 tables

  8. Characteristics of benzodiazepine receptors in rats differing in predisposition to experimental alcoholism

    International Nuclear Information System (INIS)

    Burov, Yu.V.; Maiskii, A.I.; Yukhananov, R.Yu.

    1986-01-01

    This paper studies the number and affinity of benzodiazepine receptors for diazepam in the cerebral cortex and hippocampus of rats differently predisposed to the development of experimental alcoholism. Ethanol was injected once intraperitoneally, in a dose of 2.5 g/kg. Control animals received the same volume of physiological saline. Bound and free N-methyl-tritium-diazepam were separated by means of GF/B filters. The characteristics of benzodiazepine receptors are shown in rats differing in predisposition to the development of experimental alcoholism and in rats during voluntary chronic alcoholization. It is shown that weakening of functional acitivity of the GABA-benzodiazepam complex in animals predisposed to the development of experimental alcoholism is one of the neurochemical mechanisms of development of the abstinence syndrome

  9. MR imaging for pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Syojaku, Hiroko; Nishihara, Mamiko; Sakai, Kunio; Yoshizawa, Hiroshi (Niigata Univ. (Japan). School of Medicine); Maeda, Haruo; Kurokawa, Shigeki; Yokoyama, Michio; Miura, Keiko; Tokunaga, Akiteru

    1993-11-01

    MRI examinations were performed in 20 cases of high risk obstetrics: ectopic pregnancy, fetal anomaly, pregnancy with uterine leiomyoma or ovarian tumor, and cephalopelvic disproportion. Clear useful images were obtained in 18 cases (90%). In 2 cases, however, MR images were disordered by fetal movement. Maternal sedation with diazepam was proved to be useful in suppressing fetal movement for more than 30 minutes. MRI is very useful for high risk obstetrics. (author).

  10. Suanzaoren Formulae for Insomnia: Updated Clinical Evidence and Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Qi-Hui Zhou

    2018-02-01

    Full Text Available Insomnia disorder is a widespread and refractory disease. Semen Ziziphi Spinosae, Suanzaoren, a well-known Chinese herbal medicine, has been used for treating insomnia for thousands of years. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren (FSZR for insomnia according to high-quality randomized controlled trials (RCTs and reviewed their possible mechanisms based on animal-based studies. Electronic searches were performed in eight databases from inception to November 2016. The primary outcome measures were polysomnography index and Pittsburgh sleep quality index. The secondary outcome measures were clinical effective rate and adverse events. The methodological quality of RCTs was assessed by Cochrane's collaboration tool, and only RCTs with positive for 4 out of 7 for the Cochrane risk of bias domains were included in analyses. Thirteen eligible studies with 1,454 patients were identified. Meta-analysis of high-quality RCTs showed that FSZR monotherapy was superior to placebo (P < 0.01; FSZR plus Diazepam was superior to Diazepam alone (P < 0.05; there were mixed results comparing FSZR with Diazepam (P > 0.05 or P < 0.05. Furthermore, FSZR caused fewer side effects than that of Diazepam. Suanzaoren contains complex mixtures of phytochemicals including sanjoinine A, Jujuboside A, spinosin and other flavonoids, which has sedative and hypnotic functions primarily mediated by the GABAergic and serotonergic system. In conclusion, the findings of present study supported that FSZR could be an alternative treatment for insomnia in clinic. FSZR exerted sedative and hypnotic actions mainly through the GABAergic and serotonergic system.

  11. Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice

    OpenAIRE

    Ochi, Rika; Suemaru, Katsuya; Kawasaki, Hiromu; Araki, Hiroaki

    2009-01-01

    Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline ...

  12. Behavioral properties of Balanites aegyptiaca in rodents.

    Science.gov (United States)

    Ya'u, J; Abdulmalik, U N; Yaro, A H; Chindo, B A; Anuka, J A; Hussaini, I M

    2011-06-01

    Balanites aegyptiaca is a native plant from the dry tropical areas of Africa and Arabia. It has been used in traditional medicine to treat psychoses, epilepsy, rheumatism and for the management of cough, liver and spleen conditions for many years. The plant is also used as antihelmintic and molluscicide. The present studies aimed at investigating the behavioral properties of ethanol extract of the root of this medicinal plant, which is already in common applications in the Nigerian traditional medicine. The intraperitoneal and oral mean lethal dose (LD(50)) of the extract was determined using the Lorke's method. The preliminary phytochemical screening of the extract was carried out to identify the secondary metabolites in the extract. Furthermore, the behavioral properties of the extract were evaluated using diazepam-induced sleep, open field test, staircase test and beam walking assay all in mice. The extract significantly (popen field test, the extract (150 and 300 mg/kg) and diazepam (0.05 mg/kg) produced a significant (pwalking assay the extract did not produce any significant increase in the time taken to complete task as compared to diazepam 1mg/kg which was significant at p<0.05. Furthermore, 30 mg/kg of the extract and diazepam 1mg/kg showed significant (p<0.05) mean number of foot slips, suggesting that the central nervous system depressant activity might not necessarily due to peripheral neuromuscular blockade. The result indicates that the extract of Balanites aegyptiaca possess biologically active compound(s) that have anxiolytic and sedative properties, which support the ethnomedicinal use of the plant as antipsychotic and antiepileptic agents. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).

    Science.gov (United States)

    Swedberg, M D; Jacobsen, P; Honoré, T

    1995-09-01

    The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.

  14. Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2011-01-01

    Full Text Available Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight or a placebo (solvent vehicle were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD choice test and by the Open-Field (OF exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047, while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant. The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001 but not with G. Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp., while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables. Neither dilutions of G. sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.

  15. Targeted deletion of the GABRA2 gene encoding alpha2-subunits of GABA(A) receptors facilitates performance of a conditioned emotional response, and abolishes anxiolytic effects of benzodiazepines and barbiturates.

    Science.gov (United States)

    Dixon, C I; Rosahl, T W; Stephens, D N

    2008-07-01

    Mice with point-mutated alpha2 GABA(A) receptor subunits (rendering them diazepam insensitive) are resistant to the anxiolytic-like effects of benzodiazepines (BZs) in the conditioned emotional response (CER) test, but show normal anxiolytic effects of a barbiturate. We investigated the consequence of deleting the alpha2-subunit on acquisition of the CER with increasing intensity of footshock, and on the anxiolytic efficacy of a benzodiazepine, diazepam, and a barbiturate, pentobarbital. alpha2 knockout (KO) and wildtype (WT) mice were trained in a conditioned emotional response (CER) task, in which lever pressing for food on a variable interval (VI) schedule was suppressed during the presentation of a compound light/tone conditioned stimulus (CS+) that predicted footshock. The ability of diazepam and of pentobarbital to reduce suppression during the CS+ was interpreted as an anxiolytic response. There were no differences between the genotypes in shock sensitivity, as assessed by their flinch responses to increasing levels of shock. However, alpha2 KO mice showed a greater suppression of lever pressing than WT littermates in the presence of a compound cue signalling footshock. Diazepam (0, 0.5, 1 and 2 mg/kg) induced a dose-dependent anxiolytic-like effect in WT mice but no such effect was seen in KO mice. Similarly, although pentobarbital (20 mg/kg) reduced the ability of the CS+ to reduce lever pressing rates in WT mice, this effect was not seen in the KO. These findings suggest that alpha2-containing GABA(A) receptors mediate the anxiolytic effects of barbiturates, as well as benzodiazepines, and that they may be involved in neuronal circuits underlying conditioned anxiety.

  16. Effect of acute treatment with a water-alcohol extract of Erythrina mulungu on anxiety-related responses in rats

    Directory of Open Access Journals (Sweden)

    Onusic G.M.

    2002-01-01

    Full Text Available We investigated the effect of acute oral treatment with a water-alcohol extract of the inflorescence of Erythrina mulungu (EM, Leguminosae-Papilionaceae (100, 200 and 400 mg/kg on rats submitted to different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements, the light/dark transition, and the cat odor test. These models were selected for their presumed capacity to demonstrate specific subtypes of anxiety disorders as recognized in clinical practice. Treatment with 200 mg/kg EM impaired avoidance latencies (avoidance 1 - 200 mg/kg EM: 18 ± 7 s, control group: 40 ± 9 s; avoidance 2 - 200 mg/kg EM: 15 ± 4 s, control group: 110.33 ± 38 s in a way similar to the reference drug diazepam (avoidance 1: 3 ± 0.79 s; avoidance 2: 3 ± 0.76 s, without altering escape. Additionally, the same treatments increased the number of transitions (200 mg/kg EM: 6.33 ± 0.90, diazepam: 10 ± 1.54, control group: 2.78 ± 0.60 between the two compartments and the time spent in the lighted compartment in the light/dark transition model (200 mg/kg EM: 39 ± 7 s; diazepam: 61 ± 9 s; control group: 14 ± 4 s. The dose of 400 mg/kg EM also increased this last measurement (38 ± 8 s. These results were not due to motor alterations since no significant effects were detected in the number of crossings or rearings in the arena. Furthermore, neither EM nor diazepam altered the behavioral responses of rats to a cloth impregnated with cat odor. These observations suggest that EM exerts anxiolytic-like effects on a specific subset of defensive behaviors, particularly those that have been shown to be sensitive to low doses of benzodiazepines.

  17. US Army Institute of Surgical Research Annual Research Progress Report for Fiscal Year 1991

    Science.gov (United States)

    1991-10-01

    whether growth hormone can promote anabolism in surgical patients. Patients (n=9) received a constant parenteral infusion of a hypocaloric diet which...Benzodiazepines, such as diazepam, are routinely given as premedicants for patients on a PO diet . Morphine sulfate or midazolam hydrochloride is often given as a...methionyl human growth hormone (Protropin®) in calorie-deprived human volunteers illustrated its anabolic effect. Hypocaloric parenteral nutrition

  18. The integrity of the social hierarchy in mice following administration of psychotropic drugs.

    OpenAIRE

    Poshivalov, V. P.

    1980-01-01

    1 Mice in small groups develop a despotic type of social hierarchy, a feature of which is to resist alteration through the medium of psychotropic drugs. This makes a rapid pharmacologically induced change in the social hierarchy impossible. 2 Patrolling the territory and a certain level of social interaction are both critical factors in maintaining the phenomenon of inertia in the social hierarchy. Psychotropic drugs (diazepam, droperidol and mescaline) altered both these factors to a varying...

  19. Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder

    OpenAIRE

    Finsterer, Josef; Enzelsberger, Barbara; Bastowansky, Adam

    2017-01-01

    Patient: Female, 65 Final Diagnosis: Mitochondrial disorder Symptoms: Headache ? tetanic seizure Medication: Diazepam Clinical Procedure: Admission Specialty: Neurology Objective: Challenging differential diagnosis Background: Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. Case Report: We report the case of a 65-year-old Gypsy female who was admitted for a...

  20. Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests.

    Science.gov (United States)

    Kilic, Fatma Sultan; Ismailoglu, Sule; Kaygisiz, Bilgin; Oner, Setenay

    2014-10-01

    Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders. We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats. Female Spraque-Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively. It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them. These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

  1. Intérêts et limites de l'analyse de la moelle osseuse en toxicologie médicolégale : contribution à l'interprétation quantitative des concentrations médullaires

    OpenAIRE

    Cartiser , Nathalie

    2011-01-01

    The aim of this work was to evaluate the interest of bone marrow (BM) analysis in forensic toxicology, as an alternative matrix to blood. An analytical method was developed and validated for the quantification of citalopram, diazepam, and its main metabolites (nordazepam, temazepam, oxazepam) in BM and 10 others matrices of forensic interest. This procedure was successfully applied to real cases for putrified sample analyses and to establish a tissue kinetic in rabbit samples for a pharmacoki...

  2. gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t-butylbicyclophosphorothionate binding to cerebellar granule cells

    International Nuclear Information System (INIS)

    Gallo, V.; Wise, B.C.; Vaccarino, F.; Guidotti, A.

    1985-01-01

    t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, the authors have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [ 35 S]TBPS. At 25 degrees C, and in a modified Locke solution, the [ 35 S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [ 35 S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [ 35 S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [ 35 S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [ 35 S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [ 35 S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam

  3. Altered drug binding to serum proteins in pregnant women: therapeutic relevance.

    OpenAIRE

    Perucca, E; Ruprah, M; Richens, A

    1981-01-01

    The binding of diazepam, phenytoin and valproic acid to serum proteins in vitro has been compared in pregnant women of different gestational ages and in controls. The unbound fraction of each of three drugs was elevated during pregnancy (particularly during the last 8 weeks) probably due, at least in part, to a fall in serum albumin concentration. These findings may provide a partial explanation for the increase in the clearance of certain drugs during pregnancy and need to be taken into acco...

  4. Positron-emission tomography imaging of long-term shape recognition challenges

    OpenAIRE

    Rosier, A.; Cornette, L.; Dupont, P.; Bormans, G.; Michiels, J.; Mortelmans, L.; Orban, G. A.

    1997-01-01

    Long-term visual memory performance was impaired by two types of challenges: a diazepam challenge on acquisition and a sensory challenge on recognition. Using positron-emission tomography regional cerebral blood flow imaging, we studied the effect of these challenges on regional brain activation during the delayed recognition of abstract visual shapes as compared with a baseline fixation task. Both challenges induced a significant decrease in differential activation in the left fusiform gyrus...

  5. Mitochondrial dysfunction in an animal model of diabetic neuropathy is associated with a reduction of neurosteroid synthesis. [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stephen R. Humble

    2018-03-01

    Full Text Available Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABAAR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO. This study explored the differential effect of diazepam on GABAAR modulation via neurosteroidogenesis in diabetic and wild type (WT mice. Methods: Whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from layer 2/3 cortical pyramidal neurons of the pain pathway from mice with type-II diabetic neuropathy (ob/ob and WT controls aged 60-80 days. Results: There was a key difference in the response of the WT and ob/ob cortical neurons to simultaneous incubation with diazepam and flumazenil. In contrast, diazepam and the 5a-reductase inhibitor finasteride, individually or in combination, produced the same response in both strains. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABAAR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathy, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit.

  6. Stress and suicide in the Nurses' Health Study.

    Science.gov (United States)

    Feskanich, D; Hastrup, J L; Marshall, J R; Colditz, G A; Stampfer, M J; Willett, W C; Kawachi, I

    2002-02-01

    Although stress is thought to be a risk factor for suicide, most research has been retrospective or has focused on attempted suicides or suicide ideation. This study examined prospectively the associations between self perceived stress, diazepam use, and death from suicide among adult women. A cohort study was conducted with 14 years of follow up. Stress at home and at work were assessed by questionnaire and scored on a four point scale: minimal, light, moderate, or severe. Eleven states within the United States. Female nurses (n=94 110) who were 36 to 61 years of age when they answered questions on stress and diazepam use in 1982. During 1 272 000 person years of observation 73 suicides were identified. After adjustment for age, smoking, coffee consumption, alcohol intake, and marital status, the relation between self reported stress and suicide remained U shaped. Compared with the light home and work stress categories, which had the lowest incidences of suicide, risks were increased among women reporting either severe (relative risk (RR) = 3.7, 95% confidence intervals (CI) 1.7 to 8.3) or minimal (RR=2.1, 95% CI 1.0 to 4.5) home stress and either severe (RR=1.9, 95% CI 0.8 to 4.7) or minimal (RR=2.4, 95% CI 0.9 to 6.1) work stress. When responses to home and work stress were combined, there was an almost fivefold increase in risk of suicide among women in the high stress category. Risk of suicide was over eightfold among women reporting high stress or diazepam use compared with those reporting low stress and no diazepam use. The relation between self reported stress and suicide seems to be U shaped among adult women. The excess risk for those reporting minimal stress may reflect denial or undiagnosed depression or an association with some other unmeasured risk factor for suicide.

  7. The effect of ethanol on 35-S-TBPS binding to mouse brain membranes in the presence of chloride

    International Nuclear Information System (INIS)

    Liljequist, S.; Culp, S.; Tabakoff, B.

    1989-01-01

    The effect of in vitro and in vivo administration of ethanol on the binding of 35 S-t-butyl-bicyclophosphorothionate ( 35 S-TBPS) to cortical brain membranes of C57B1 mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal 35 S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on 35 S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of 35 S-TBPS binding produced by diazepam. 35 S-TBPS binding to cortical brain membranes was inhibited by the putative Cl - channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (≤ 100 mM ethanol). Chronic ethanol ingestion in vivo, which produced tolerance to and physical dependence on ethanol in the animals, did not alter the stimulatory and inhibitory effects of GABA and pentobarbital on 35 S-TBPS binding. The enhancement of 35 S-TBPS binding produced by diazepam was slightly, but significantly, enhanced in brain membranes from animals which had undergone 24 hours of ethanol withdrawal. Chronic ethanol treatment did not change the potency of picrotoxin and of the peripheral BDZ-receptor ligand RO 5-4864 to competitively inhibit 35 S-TBPS binding. Our results suggest that in vitro addition of ethanol alters the activity of the activity of the GABA benzodiazepine (BDZ) receptor complex. Although there was no change in basal 35 S-TBPS binding following chronic in vivo ethanol administration, our curent data suggest that chronic ethanol ingestion may cause specific changes of the GABA BDZ receptor proteins, in this study revealed as an altered modulation of 35 S-TBPS binding by diazepam. (author)

  8. The effect of ethanol on sup 35 -S-TBPS binding to mouse brain membranes in the presence of chloride

    Energy Technology Data Exchange (ETDEWEB)

    Liljequist, S.; Culp, S.; Tabakoff, B. (Laboratory for Studies of Neuroadaptive Processes, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda (USA))

    1989-01-01

    The effect of in vitro and in vivo administration of ethanol on the binding of {sup 35}S-t-butyl-bicyclophosphorothionate ({sup 35}S-TBPS) to cortical brain membranes of C57B1 mice was investigated using KCl containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal {sup 35}S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action on {sup 35}S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of {sup 35}S-TBPS binding produced by diazepam. {sup 35}S-TBPS binding to cortical brain membranes was inhibited by the putative Cl{sup -} channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol. Chronic ethanol ingestion in vivo, which produced tolerance to and physical dependence on ethanol in the animals, did not alter the stimulatory and inhibitory effects of GABA and pentobarbital on {sup 35}S-TBPS binding. The enhancement of {sup 35}S-TBPS binding produced by diazepam was slightly, but significantly, enhanced in brain membranes from animals which had undergone 24 hours of ethanol withdrawal. Chronic ethanol treatment did not change the potency of picrotoxin and of the peripheral BDZ-receptor ligand RO 5-4864 to competitively inhibit {sup 35}S-TBPS binding. Our results suggest that in vitro addition of ethanol alters the activity of the activity of the GABA benzodiazepine (BDZ) receptor complex. Although there was no change in basal {sup 35}S-TBPS binding following chronic in vivo ethanol administration, our curent data suggest that chronic ethanol ingestion may cause specific changes of the GABA BDZ receptor proteins, in this study revealed as an altered modulation of {sup 35}S-TBPS binding by diazepam.

  9. Human iPSC-Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

    Science.gov (United States)

    2015-10-01

    1) Induction of status epilepticus (SE) in young rats through kainic acid injections to generate rats exhibiting chronic TLE typified by SRS. (2...of status epilepticus (SE) via graded kainic acid injections, termination of acute seizures 2 hours after SE onset via diazepam injections and...injections to these rats to induce acute seizures or status epilepticus (SE) in 11 separate experimental sessions (n=8-12/session). These experiments

  10. The Efficacy of LY293558 in Blocking Seizures and Associated Morphological, and Behavioral Alterations Induced by Soman in Immature Male Rats and the Role of the M1 Muscarinic Acetylcholine Receptor in Organophosphate Induced Seizures

    Science.gov (United States)

    2015-01-30

    including seizures or status epilepticus (SE), and if left untreated results in long-term brain damage and neuropsychiatric symptoms or death. OPs...118 Abstract Exposure to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the presently...inhibition in the brain produces convulsive seizures and status epilepticus (SE), initiated by the excessive stimulation of cholinergic receptors. If

  11. Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water.

    Science.gov (United States)

    Moretti, Matteo; Andrello, Luisa; Visonà, Silvia; Vignali, Claudia; Groppi, Angelo; Freni, Francesca; Osculati, Antonio; Tajana, Luca; Morini, Luca

    2018-04-15

    The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

    Science.gov (United States)

    Calas, André-Guilhem; Perche, Olivier; Richard, Olivier; Perche, Astrid; Pâris, Arnaud; Lauga, Fabien; Herzine, Ameziane; Palomo, Jennifer; Ardourel, Marie-Yvonne; Menuet, Arnaud; Mortaud, Stéphane; Pichon, Jacques; Montécot-Dubourg, Céline

    2016-05-04

    Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.

  13. Conscious sedation for patients undergoing enteroclysis: Comparing the safety and patient-reported effectiveness of two protocols

    International Nuclear Information System (INIS)

    Maglinte, Dean D.T.; Applegate, Kimberly E.; Rajesh, Arumugam; Jennings, S. Gregory; Ford, Jason M.; Savabi, Mojgan Sarah; Lappas, John C.

    2009-01-01

    Objective: To compare the safety and patient-reported effectiveness of two regimens for conscious sedation during enteroclysis. Materials and methods: We surveyed two groups of outpatients and retrospectively reviewed procedure records for conscious sedation and complications. Patients were divided into Group One (received sedative/amnesic diazepam), and Group Two, (received amnesic/sedative, midazolam and analgesic fentanyl). Results: All enteroclyses were successfully completed; there were no hospital admissions due to complications. In Group One (n = 106), mean dose of diazepam was 12.7 mg. 25% had oxygen desaturation (n = 25), and post-procedure vomiting without aspiration (n = 1). 56% of outpatients completed phone surveys, and 68% recalled procedural discomfort. In Group Two (n = 45), mean doses were 3.9 mg midazolam and 108 mcg fentanyl. 31% had desaturation (n = 13), and post-procedure vomiting without aspiration (n = 1). 87% had only a vague recall of the procedure or of any discomfort. Conclusion: A combination of amnesic and fentanyl prevented the recall of discomfort of nasoenteric intubation and infusion in most patients who had enteroclysis compared to diazepam. Most of the patients would undergo the procedure again, if needed.

  14. Conscious sedation for patients undergoing enteroclysis: Comparing the safety and patient-reported effectiveness of two protocols

    Energy Technology Data Exchange (ETDEWEB)

    Maglinte, Dean D.T. [Department of Radiology, Indiana University Medical Center, 550 N, University Boulevard, University Hospital Room 0279, Indianapolis, IN 46202-5253 (United States)], E-mail: dmaglint@iupui.edu; Applegate, Kimberly E.; Rajesh, Arumugam; Jennings, S. Gregory; Ford, Jason M. [Department of Radiology, Indiana University Medical Center, 550 N, University Boulevard, University Hospital Room 0279, Indianapolis, IN 46202-5253 (United States); Savabi, Mojgan Sarah [Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, 550 N, University Boulevard, Indianapolis, IN 46202-5253 (United States); Lappas, John C. [Department of Radiology, Indiana University Medical Center, 550 N, University Boulevard, University Hospital Room 0279, Indianapolis, IN 46202-5253 (United States)

    2009-06-15

    Objective: To compare the safety and patient-reported effectiveness of two regimens for conscious sedation during enteroclysis. Materials and methods: We surveyed two groups of outpatients and retrospectively reviewed procedure records for conscious sedation and complications. Patients were divided into Group One (received sedative/amnesic diazepam), and Group Two, (received amnesic/sedative, midazolam and analgesic fentanyl). Results: All enteroclyses were successfully completed; there were no hospital admissions due to complications. In Group One (n = 106), mean dose of diazepam was 12.7 mg. 25% had oxygen desaturation (n = 25), and post-procedure vomiting without aspiration (n = 1). 56% of outpatients completed phone surveys, and 68% recalled procedural discomfort. In Group Two (n = 45), mean doses were 3.9 mg midazolam and 108 mcg fentanyl. 31% had desaturation (n = 13), and post-procedure vomiting without aspiration (n = 1). 87% had only a vague recall of the procedure or of any discomfort. Conclusion: A combination of amnesic and fentanyl prevented the recall of discomfort of nasoenteric intubation and infusion in most patients who had enteroclysis compared to diazepam. Most of the patients would undergo the procedure again, if needed.

  15. Do not overlook acute isoniazid poisoning in children with status epilepticus.

    Science.gov (United States)

    Caksen, Hüseyin; Odabas, Dursun; Erol, Mehmet; Anlar, Omer; Tuncer, Oguz; Atas, Bülent

    2003-02-01

    A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.

  16. Motivational drive and alprazolam misuse: A recipe for aggression?

    Science.gov (United States)

    Albrecht, Bonnie; Staiger, Petra K; Hall, Kate; Kambouropoulos, Nicolas; Best, David

    2016-06-30

    Benzodiazepine-related aggression has received insufficient research attention, in particular little is known about the motivational factors which may contribute to the development of this paradoxical response. The revised Reinforcement Sensitivity Theory provides a theoretical framework from which to understand the relevant underlying motivational processes. The current study aimed to identify the role of approach and avoidance motivational tendencies in the occurrence of benzodiazepine-related aggression. Data regarding benzodiazepine and other substance use, approach and avoidance motivation, and general and physical aggressive behaviour were collected via self-report questionnaires. Participants were a convenience sample (n=204) who reported using benzodiazepines in the previous year. Participants were primarily male (62.7%), aged 18-51 years old. Hierarchical multiple regressions indicated that general and physical aggression were predicted by alprazolam use and Drive, a facet of approach motivation. Overall, lower diazepam use significantly predicted higher levels of general aggression. However, when diazepam-preferring participants were examined in isolation of the larger sample (23.5% of sample), problematic (dependent) diazepam use was associated with greater aggression scores, as was dependence risk for alprazolam-preferring participants (39.7% of sample). The findings highlight the importance of motivational factors and benzodiazepine use patterns in understanding benzodiazepine-related aggression, with implications for violent offender rehabilitation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Radioimmunoassay of serum T3, T4 and TSH during anesthesia and operation

    International Nuclear Information System (INIS)

    Gosheva-Antonova, Ts.; Zakharieva, B.; Kurtev, I.

    1987-01-01

    The serum concentrations of thyroxine (T 3 ), triiodothyronine (T 4 ) and thyroid-stimulating hormone (TSH) were determined in 31 partients before and during urologic operations on the 30th and 60th minute since the onset of the operation, performed under endotracheal halotane or neuroleptanesthesia (NLA) in assisted breathing and intravenous drip anesthesia with ketalar-diazepam in spontaneous breathing. There was statistically significant rise in T 4 level, decrease in T 3 and negligible changes in TSH level, in patients operated under halotane anesthesia. In those operated under NLA, T 4 tended initially to be elevated, with subseguent fall to starting level, with a tendency toward rise in TSH and stable unchanged T 3 level. Ketalar-diazepam anesthesia was applied only to patients subjected to transurethral resections. T 4 in them tended to be decreased, while T 3 and TSH showed negligible changes. Since the operations of patients anesthesized with halotane and NLA had similar localizations and severity, the differences in the thyroid hormone reactions could be associated with the type of anesthesia. The negligible changes in TSH are highly suggestive that this hormone is not influenced by the operation stress and anesthetics, and does hot exert regulating effect upon the thyroid status under these conditions. The milder reactions in patients operated under ketalar-diazepam anestesia may largely be associated with the milder operation stress in transurethal resection

  18. Antioxidant effects of nerolidol in mice hippocampus after open field test.

    Science.gov (United States)

    Nogueira Neto, José Damasceno; de Almeida, Antonia Amanda Cardoso; da Silva Oliveira, Johanssy; Dos Santos, Pauline Sousa; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2013-09-01

    The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

  19. Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Basile, A.S.; Pannell, L.; Jaouni, T.; Gammal, S.H.; Fales, H.M.; Jones, E.A.; Skolnick, P.

    1990-01-01

    Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans

  20. Efficacy and safety of non-intravenous midazolam for the treatment of status epilepticus in children: a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Yan LIN

    2016-02-01

    Full Text Available Objective To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE in children.  Methods Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI, VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software. Results There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1 midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290. However, non-intravenous (intranasal or buccal midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020. 2 The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070. 3 There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170. 4 There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500.  Conclusions Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the

  1. Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata).

    Science.gov (United States)

    Thakur, Ajit Kumar; Chatterjee, Shyam Sunder; Kumar, Vikas

    2015-01-01

    Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. ( chuān xīn lián), a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11(th) day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5(th) day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d) or diazepam (5 mg/kg/d). Benzodiazepine-like potentiation of pentobarbital hypnosis was observed in andrographolide-treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses.

  2. Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors.

    Science.gov (United States)

    Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol

    2013-08-01

    Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats.

    Science.gov (United States)

    Stojicić, S; Milutinović-Smiljanić, S; Sarenac, O; Milosavljević, S; Paton, J F R; Murphy, D; Japundzić-Zigon, N

    2008-04-01

    To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF(BP) oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V(1a), V(1b) and V(2) receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V(1b) receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.

  4. PRELIMINARY STUDIES ON THE BEHAVIOURAL EFFECTS OF THE METHANOL EXTRACT OF LEONOTIS NEPETIFOLIA LINN STEM IN MICE

    Science.gov (United States)

    Ayanwuyi, Lydia O.; Kwanashie, Helen O.; Hussaini, Isa M.; Yaro, Abdullahi H.

    2016-01-01

    Background: Leonotis nepetifolia Linn (Lamiaceae) is used in traditional medicine for its calming (tranquilizing) effects. The aim of this study was to determine whether there is any scientific justification for this use. To achieve this purpose, we investigated the behavioural effects of the methanol extract of Leonotis nepetifolia stem (37.5, 75 and 150 mg/kg) in mice. Methods: Acute toxicity studies were carried out on the methanol stem extract of Leonotis nepetifolia to determine the LD50. The behavioural tests employed were diazepam-induced sleep onset and duration, hole board assay for exploratory activity, mouse beam walk assay for motor coordination, and the staircase test for the detection of anxiolytic compounds. Preliminary phytochemical screening was also carried out on the extract. Results: The intraperitoneal LD50 value was found to be 3.8 g/kg. The results showed that the extract significantly prolonged the duration of diazepam-induced sleep at the highest dose (150 mg/kg). There was no observable effect on exploratory activity and motor coordination at the doses tested (37.5, 75 and 150 mg/kg). The extract, however, at 150 mg/kg elicited a significant decrease in the number of rearings in the staircase test, an effect also observed in the group of mice injected with an anxiolytic dose of diazepam. The preliminary phytochemical screening revealed the presence of alkaloids, saponins, glycosides and triterpenoids. Conclusion: The results obtained suggest that the crude methanol extract of Leonotis nepetifolia stem possesses some biologically active constituents with potential anxiolytic activity and thus may justify its traditional use as a tranquilizer. PMID:28852715

  5. Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata

    Directory of Open Access Journals (Sweden)

    Ajit Kumar Thakur

    2015-01-01

    Full Text Available Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F. Wall. Ex. Nees. (穿心蓮 chuān xīn lián, a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11th day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5th day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d or diazepam (5 mg/kg/d. Benzodiazepine-like potentiation of pentobarbital hypnosis was observed in andrographolide-treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses.

  6. Preventive Effects of Forced Exercise against Alcohol-induced Physical Dependency and Reduction of Pain Perception Threshold

    Directory of Open Access Journals (Sweden)

    Majid Motaghinejad

    2014-01-01

    Full Text Available Background: Treatment of postabstinence syndrome of alcohol is one of the major strategies of alcoholism treatment. Exercise can be modulated major brain pathways such as a reward system and pain perception centers. The aim of this study was to evaluation the effects of forced exercise in the management of alcohol dependence and pain perception alteration which induced by alcoholism. Methods: 72 adult male rats were divided into 2 major groups: (1 40 of them was divided into groups of positive control (alcohol dependent negative control and alcohol dependent groups under treatment by forced exercise, diazepam (0.4 mg/kg and forced exercise in combination with diazepam and alcohol withdrawal signs, and blood cortisols, were measured in this groups. (2 32 rats were divided into control, alcohol dependent (without treatment, and alcohol-dependent groups under treatment by forced exercise or indometacin (5 mg/kg and then pain perception was assessed by using writhing test, tail-flick and hot plate test. Results: Forced exercise, diazepam, and their combinations significantly attenuates withdrawal syndrome to 20 ± 2, 22 ± 1.3 and 16 ± 2 and blood cortisol level to 6.8 ± 1.3,7.9 ± 1.2 and 5.8 ± 1.1, respectively, in comparison with the positive control group (P < 0.05 and P < 0.001. In alcohol dependent animal under treatment by forced exercise, pain response significantly inhibited with 37%, 57% and 38% decreases in writhing test, hot plate, and tail-flick test, respectively, in comparison with alcohol dependent (without treatment group (P < 0.05. Conclusions: This study suggested that forced exercise can be useful as adjunct therapy in alcoholism patient and also can be effective in modulation of pain threshold reduction that was induced by alcohol dependency.

  7. Central depressant activity of butanol fraction of Securinega virosa root bark in mice.

    Science.gov (United States)

    Magaji, Mohammed Garba; Yaro, Abdullahi Hamza; Musa, Aliyu Muhammad; Anuka, Joseph Akponso; Abdu-Aguye, Ibrahim; Hussaini, Isa Marte

    2012-05-07

    Securinega virosa is a commonly used medicinal plant in African traditional medicine in the management of epilepsy and mental illness. Previous studies in our laboratory showed that the crude methanol root bark extract of the plant possesses significant behavioral effect in laboratory animals. In an attempt to isolate and characterize the biological principles responsible for the observed activity, this study is aimed at evaluating the central depressant activity of the butanol fraction of the methanol root bark extract of Securinega virosa. The medial lethal dose of the butanol fraction was estimated using the method of Lorke. Preliminary phytochemical screening was conducted on the butanol fraction using standard protocol. The behavioral effect of the butanol fraction (75, 150 and 300mg/kg) was evaluated using diazepam induced sleep test, hole-board test, beam walking assay, staircase test, open field test and elevated plus maze assay, all in mice. The median lethal dose of the butanol fraction was estimated to be 1256.9mg/kg. The preliminary phytochemical screening revealed the presence of tannins, saponins, alkaloids, flavonoids, cardiac glycosides, similar to those found in the crude methanol extract. The butanol fraction significantly (Ptime taken to complete the task and number of foot slips in the beam walking assay, suggesting that it does not induce significant motor coordination deficit. Diazepam (2mg/kg), the standard agent used significantly (Popen field test, the butanol fraction significantly reduced the number of square crossed as well as the number of rearing. However, the butanol fraction did not significantly alter the behavior of mice in the elevated plus maze assay, while diazepam (0.5mg/kg) significantly (Ptime spent in the open arm and reduced the number of closed arm entry. The findings of this study suggest that the butanol fraction of Securinega virosa root bark contains some bioactive principles that are sedative in nature. Copyright

  8. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine

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    Catherine E. Creeley

    2013-07-01

    Full Text Available Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and several drugs, including alcohol, that are abused by pregnant women, trigger widespread neuroapoptosis in the developing brain of several animal species, including non-human primates. Caffeine (CAF is often administered to premature infants to stimulate respiration, and these infants are also exposed simultaneously to anesthetic drugs for procedural sedation and/or surgical procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may heavily consume CAF. We administered CAF to infant mice alone or in combination with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which are drugs of abuse and/or drugs frequently used in pediatric medicine, and found that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the neuroapoptogenic action of each of these other drugs. Exposure of infant mice to CAF + phencyclidine resulted in long-term impairment in behavioral domains relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF + diazepam resulted in long-term learning/memory impairment. At doses used in these experiments, these behavioral impairments either did not occur or were substantially less pronounced in mice exposed to CAF alone or to phencyclidine or diazepam alone. CAF currently enjoys the reputation of being highly beneficial and safe for use in neonatal medicine. Our data suggest the need to consider whether CAF may have harmful as well as beneficial effects on the developing brain, and the need for research aimed at understanding the full advantage of its beneficial effects while avoiding its potentially harmful effects.

  9. Effect of Erythrina velutina and Erythrina mulungu in rats submitted to animal models of anxiety and depression

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    M.D. Ribeiro

    2006-02-01

    Full Text Available Erythrina velutina (EV and Erythrina mulungu (EM, popularly used in Brazil as tranquilizing agents, were studied. The effects of acute and chronic oral treatment with a water:alcohol extract of EV (7:3, plant grounded stem bark; acute = 100, 200, 400 mg/kg; chronic = 50, 100, 200 mg/kg were evaluated in rats (N = 11-12 submitted to the elevated T-maze (for avoidance and escape measurements model of anxiety. This model was selected for its presumed capacity to elicit specific subtypes of anxiety disorders recognized in clinical practice: avoidance has been related to generalized anxiety and escape to panic. Additionally, animals were treated with the same doses of EV and EM (water:alcohol 7:3, inflorescence extract and submitted to the forced swim test for the evaluation of antidepressant activity (N = 7-10. Both treatment regimens with EV impaired elevated T-maze avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (avoidance 1, mean ± SEM, acute study: 131.1 ± 45.5 (control, 9.0 ± 3.3 (diazepam, 12.7 ± 2.9 (200 mg/kg, 28.8 ± 15.3 (400 mg/kg; chronic study: 131.7 ± 46.9 (control, 35.8 ± 29.7 (diazepam, 24.4 ± 10.4 (50 mg/kg, 29.7 ± 11.5 (200 mg/kg. Neither EV nor EM altered measurements performed in the forced swim test, in contrast to the reference drug imipramine that significantly decreased immobility time after chronic treatment. These results were not due to motor alterations since no significant effects were detected in an open field. These observations suggest that EV exerts anxiolytic-like effects on a specific subset of defensive behaviors which have been associated with generalized anxiety disorder.

  10. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

    International Nuclear Information System (INIS)

    Hatano, V.Y.; Torricelli, A.S.; Giassi, A.C.C.; Coslope, L.A.; Viana, M.B.

    2012-01-01

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer

  11. Participation of the GABAergic system in the anesthetic effect of Lippia alba (Mill.) N.E. Brown essential oil

    Energy Technology Data Exchange (ETDEWEB)

    Heldwein, C.G.; Silva, L.L. [Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Reckziegel, P. [Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Barros, F.M.C. [Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Bürger, M.E.; Baldisserotto, B. [Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Mallmann, C.A. [Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Schmidt, D.; Caron, B.O. [Departamento de Ciências Agronômicas e Ambientais, Universidade Federal de Santa Maria, Campus de Frederico Westphalen, Frederico Westphalen, RS (Brazil); Heinzmann, B.M. [Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2012-04-05

    The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABA{sub A} receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABA{sub A} receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish.

  12. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, V.Y.; Torricelli, A.S. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil); Giassi, A.C.C. [Cellular and Molecular Medicine, University of Ottawa, Ottawa (Canada); Coslope, L.A. [Parque Nacional da Chapada Diamantina, Chapada Diamantina, BA (Brazil); Viana, M.B. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil)

    2012-02-27

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  13. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

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    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  14. Experimental research on the interactions between some anxiolytics and dietary sodium monoglutamate

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    Buzescu Anca

    2014-12-01

    Full Text Available Objectives: Monosodium glutamate, the salt of glutamic acid, is largely used as a flavour enhancer (E621. In this study, we determine if monosodium glutamate, after repeated oral administration, can induce any degree of anxiety. Taking into account the interdependence between glutamate and GABA neurotransmissions, we studied the possible interactions of monosodium glutamate with some representatives belonging to benzodiazepines therapeutical class, diazepam and alprazolam, used as first line therapy for the treatment of anxiety. Methods: For determining the degree of anxiety, the specific cross-labyrinth test was used. The medium time spent in the closed-arms of the crosslabyrinth is correlated with increased anxiety and the medium time spent in the opened arms is correlated with a low degree anxiety. NMRI adult mice received 300 mg/kg monosodium glutamate for 21 days, dose representing 1/50 from mice LD50 (15000mg/kg and twice the maximum admitted dose/ day for human. Results: When compared to control group, the group receiving monosodium glutamate, showed a not statistically significant slight increase in the degree of anxiety. The groups receiving benzodiazepines presented a significant reduction of the degree of anxiety, proving their anxiolytic effect. The groups receiving glutamate and diazepam or alprazolam, showed a lower reduction of the degree of anxiety, than group receiving only benzodiazepines, phenomenon which proves an antagonism between glutamate and the anxiolytics used in this study. Conclusions: The oral administration of monosodium glutamate increases slightly, not statistically significant, the degree of anxiety in mice and significantly alters the response to the benzodiazepines therapy, reducing the effect for both alprazolam and diazepam.

  15. Evaluation of Ashwagandha in alcohol withdrawal syndrome

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    Ruby B

    2012-10-01

    Full Text Available Objective: To evaluate the effect of Ashwagandha (ASW in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg in comparison with diazepam (1 mg/kg in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ kindling test for seizure threshold, forced swim test (FST for depression and locomotor activity (LCA in open field test (OFT. 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p. In FST, mice were forced to swim and the total duration of immobility (seconds was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions.

  16. Electrocardiographic Manifestations of Benzodiazepine Toxicity

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    Nahid Kazemzadeh

    2014-11-01

    Full Text Available Background: The aim of this study was to evaluate and compare the clinical and electrocardiographic (ECG manifestations of benzodiazepines (BZs. Methods: In this retrospective study, all BZ-poisoned patients hospitalized at Loghman Hakim Hospital between September 2010 and March 2011 were evaluated. Patients’ information including age, sex, time elapsed between the ingestion and presentation, and type of the BZ used were extracted from the patients' charts and recorded. ECGs on presentation to the emergency department (ED were evaluated and parameters such as PR interval, QRS duration, corrected QT, amplitude of S wave in lead I, height of R wave and R/S ratio in the lead aVR were also measured and recorded. Results: Oxazepam, chlordiazepoxide, lorazepam, alprazolam, diazepam, and clonazepam were ingested by 9 (3%, 13 (4.4%, 29 (9.9%, 105 (35.8%, 65 (22.2%, and 72 (24.6% patients, respectively. Mean PR interval was reported to be 0.16 ± 0.03 sec and PR interval of greater than 200 msec was detected in 12 (4.5% patients. Mean QRS duration was 0.07 ± 0.01sec and QRS≥120 msec was observed in 7 (2.6% cases. Conclusion: Diazepam is the only BZ that does not cause QRS widening and oxazepam is the only one not causing PR prolongation. It can be concluded that if a patient refers with a decreased level of consciousness and accompanying signs of BZ toxicity, QRS widening in ECG rules out diazepam, whereas PR prolongation rules out oxazepam toxicity.

  17. Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

    International Nuclear Information System (INIS)

    Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

    1988-01-01

    The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted)

  18. Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators

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    Andres D. Ramirez

    2013-12-01

    Full Text Available Dual orexin receptor antagonists (DORAs are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA-A receptor modulators of distinct chemical structure and pharmacologic properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam (0.3–30 mg/kg administered orally [PO] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25–1.25 g/kg induced impairment on the rotarod. By contrast, neither DORA-12 (10–100 mg/kg, PO nor almorexant (30–300 mg/kg, PO impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone and diazepam and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development.

  19. Participation of the GABAergic system in the anesthetic effect of Lippia alba (Mill.) N.E. Brown essential oil

    International Nuclear Information System (INIS)

    Heldwein, C.G.; Silva, L.L.; Reckziegel, P.; Barros, F.M.C.; Bürger, M.E.; Baldisserotto, B.; Mallmann, C.A.; Schmidt, D.; Caron, B.O.; Heinzmann, B.M.

    2012-01-01

    The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABA A receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABA A receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish

  20. Blood-brain barrier in vitro models as tools in drug discovery: assessment of the transport ranking of antihistaminic drugs.

    Science.gov (United States)

    Neuhaus, W; Mandikova, J; Pawlowitsch, R; Linz, B; Bennani-Baiti, B; Lauer, R; Lachmann, B; Noe, C R

    2012-05-01

    In the course of our validation program testing blood-brain barrier (BBB) in vitro models for their usability as tools in drug discovery it was evaluated whether an established Transwell model based on porcine cell line PBMEC/C1-2 was able to differentiate between the transport properties of first and second generation antihistaminic drugs. First generation antihistamines can permeate the BBB and act in the central nervous system (CNS), whereas entry to the CNS of second generation antihistamines is restricted by efflux pumps such as P-glycoprotein (P-gP) located in brain endothelial cells. P-gP functionality of PBMEC/C1-2 cells grown on Transwell filter inserts was proven by transport studies with P-gP substrate rhodamine 123 and P-gP blocker verapamil. Subsequent drug transport studies with the first generation antihistamines promethazine, diphenhydramine and pheniramine and the second generation antihistamines astemizole, ceterizine, fexofenadine and loratadine were accomplished in single substance as well as in group studies. Results were normalised to diazepam, an internal standard for the transcellular transport route. Moreover, effects after addition of P-gP inhibitor verapamil were investigated. First generation antihistamine pheniramine permeated as fastest followed by diphenhydramine, diazepam, promethazine and second generation antihistaminic drugs ceterizine, fexofenadine, astemizole and loratadine reflecting the BBB in vivo permeability ranking well. Verapamil increased the transport rates of all second generation antihistamines, which suggested involvement of P-gP during their permeation across the BBB model. The ranking after addition of verapamil was significantly changed, only fexofenadine and ceterizine penetrated slower than internal standard diazepam in the presence of verapamil. In summary, permeability data showed that the BBB model based on porcine cell line PBMEC/C1-2 was able to reflect the BBB in vivo situation for the transport of

  1. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  2. Iomazenil: pharmacological and animal data

    International Nuclear Information System (INIS)

    Beer, H.F.; Blaeuenstein, P.A.; Hasler, P.H.; Schubiger, P.A.; Hunkeler, W.; Bibettu, E.P.; Pieri, L.; Grayson Richards, J.

    1990-01-01

    The flumazenil analogue Ro 16-0154 (Iomazenil), a benzodiazepine partial inverse agonist, has been labelled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in human brain. The purified 123 I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacological properties were comparable to those of flumazenil with the exception of the antagonism of diazepam versus pentylenetetrazol. Biodistribution in rats (1 h p.i.) resulted in a high brain to blood ratio of 16. Clinical studies revealed images of the bezodiazepine receptor density in the brain. (author) 9 figs., 3 tabs., 27 refs

  3. Coumarin Compounds of Biebersteinia Multifida Roots Show Potential Anxiolytic Effects In Mice

    Directory of Open Access Journals (Sweden)

    Hamid Reza Monsef-Esfahani

    2013-06-01

    Full Text Available Background:Traditional preparations of the root of Biebersteinia multifida DC (Geraniaceae, a native medicinal plant of Irano-Turanian floristic region, have been used for the treatment of phobias as anxiolytic herbal preparation.Methods:We utilized the phobic behavior of mice in an elevated plus-maze as a model to evaluate the anxiolytic effect of the plant extract and bio-guided fractionation was applied to isolate the active compounds. Total root extract, alkaline and ether fraction were administered to mice at different doses 30 and 90 min prior to the maze test. Saline and diazepam were administered as negative and positive controls, respectively. The time spent in open and closed arms, an index of anxiety behavior and entry time, was measured as an index of animal activity.Results:The total root extract exhibited anxiolytic effect which was comparable to diazepam but with longer duration. This sustained effect of the crude extract was sustained for 90 min and was even more after injection of 45 mg/kg while the effect of diazepam had been reduced by 90 min. The anxiolytic effect factor was only present in the alkaline fraction and displayed its effect at lower doses than diazepam while pure vasicinone as the previously known alkaloid did not shown anxiolytic effect. The effect of the alkaline fraction was in a dose dependent manner starting at 0.2 mg/kg with a maximum at 1.0 mg/kg. Bio-guided fractionation using a variety of chromatographic methods led to isolation and purification of three coumarin derivatives from the bioactive fraction, including umbelliferone, scopoletin, and ferulic acid.Conclusion:For the first time, bio-guided fractionation of the root extract of B. multifida indicates significant sustained anxiolytic effects which led to isolation of three coumarin derivatives with well-known potent MAO inhibitory and anti-anxiety effects. These data contribute to evidence-based traditional use of B. multifida root for anxiety

  4. Comparison of anesthetic agents in the sea otter

    Energy Technology Data Exchange (ETDEWEB)

    Williams, T.D.; Kocher, F.H.

    1978-01-01

    Five anesthetic agents (CI744, etorphine, fentanyl, ketamine hydrochloride, and halothane) were tested to establish the dosage of a safe, effective, short-acting anesthetic for use in the sea otter. Etorphine, at a dosage of 0.75 mg per adult otter and used in conjunction with diazepam, at a dosage of 1.25 mg per adult otter, met most of the requirements for use under field conditions. Halothane, administered through an anesthetic machine, proved to be effective for use in a veterinary hospital.

  5. Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.

    Science.gov (United States)

    Wesołowska, Anna; Nikiforuk, Agnieszka

    2007-04-01

    The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.

  6. Opioid receptor mediated anticonvulsant effect of pentazocine.

    Science.gov (United States)

    Khanna, N; Khosla, R; Kohli, J

    1998-01-01

    Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

  7. Prophylactic drug management for febrile seizures in children

    Directory of Open Access Journals (Sweden)

    Martin Offringa

    , intermittent phenobarbitone or ibuprofen versus placebo or no treatment was found; nor for diclofenac versus placebo followed by ibuprofen, acetominophen or placebo; nor for intermittent rectal diazepam versus intermittent valproate, nor phenobarbitone versus intermittent rectal diazepam. AUTHORS' CONCLUSIONS No clinically important benefits for children with febrile seizures were found for intermittent oral diazepam, phenytoin, phenobarbitone, intermittent rectal diazepam, valproate, pyridoxine, intermittent phenobarbitone or intermittent ibuprofen, nor for diclofenac versus placebo followed by ibuprofen, acetominophen or placebo. Adverse effects were reported in up to 30% of children. Apparent benefit for clobazam treatment in one recent trial needs to be replicated to be judged reliable. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management and, most importantly, the benign nature of the phenomenon.

  8. Nanoemulsões como sistemas de liberação parenteral de fármacos

    Directory of Open Access Journals (Sweden)

    Fernanda Bruxel

    2012-01-01

    Full Text Available Lipid nanoemulsions have recently been proposed as parenteral delivery systems for poorly-soluble drugs. These systems consist of nanoscale oil/water dispersions stabilized by an appropriate surfactant system in which the drug is incorporated into the oil core and/or adsorbed at the interface. This article reviews technological aspects of such nanosystems, including their composition, preparation methods, and physicochemical properties. From this review, it was possible to identify five groups of nanoemulsions based on their composition. Biopharmaceutical aspects of formulations containing some commercially available drugs (diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1 were then discussed.

  9. The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.

    Science.gov (United States)

    Lee, Dawn; Gladwell, Daniel; Batty, Anthony J; Brereton, Nic; Tate, Elaine

    2013-04-01

    In the UK, two treatment options are used for acute epileptic seizures in the community-rectal diazepam and unlicensed buccal midazolam. In practice, the former is rarely used, with unlicensed buccal midazolam being widely recommended and prescribed by physicians. In September 2011, Buccolam(®) (licensed midazolam oromucosal solution) became the first medicine to receive a Paediatric-Use Marketing Authorization (PUMA) and it is indicated for the treatment of prolonged, acute, convulsive seizures by caregivers in the community for children (aged 6 months to marketing authorization processes and may be based upon small population subsets and may not, in some cases, require new safety or efficacy data to be generated; a similar situation to that seen for orphan drugs. This can lead to challenges when conducting economic evaluations. The aim of this study was to assess the cost effectiveness of Buccolam(®) for children with a diagnosis of epilepsy suffering prolonged, acute, convulsive seizures occurring in the UK community setting. DESIGN AND PERSPECTIVE: A hybrid model was developed according to a UK payer perspective. The model included a time-to-event simulation for the frequency and location of occurrence of seizures, along with a decision-tree model that assessed the treatment pathway when a seizure occured. The model compared treatment with Buccolam(®) with standard care in the community (95 % unlicensed buccal midazolam and 5 % rectal diazepam) or either treatment alone. The model was informed by data from a variety of sources, including clinical effectiveness estimates, and costs based on published UK data, using 2012-13 prices, where possible. To determine current practice and real-world effectiveness, a Delphi panel and a survey of parents of children with epilepsy were conducted. Buccolam(®) showed a reduction in costs of £2,939 compared with standard care, £14,269 compared with rectal diazepam alone and £886 compared with unlicensed buccal midazolam

  10. Disruption of the acyl-coa binding protein gene delays hepatic adaptation to metabolic changes at weaning

    DEFF Research Database (Denmark)

    Neess, Ditte; Bloksgaard, Maria; Sørensen, Signe Bek

    2011-01-01

    The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an intracellular protein that binds C14-C22 acyl-CoA esters and is thought to act as an acyl-CoA transporter. In vitro analyses have indicated that ACBP can transport acyl-CoA esters between different enzymatic systems; however....... The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads...

  11. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  12. Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers.

    Science.gov (United States)

    Polepally, Akshanth R; King, Jennifer R; Ding, Bifeng; Shuster, Diana L; Dumas, Emily O; Khatri, Amit; Chiu, Yi-Lin; Podsadecki, Thomas J; Menon, Rajeev M

    2016-08-01

    The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were ≤25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by ≤40 and ≤46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by ≤25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose

  13. Drug use among Nigerian university students: prevalence of self-reported use and attitudes to use.

    Science.gov (United States)

    Nevadomsky, J J

    1985-01-01

    Based on a sample of nearly 300 university students in Benin City, Nigeria, the present study shows that, although a wide range of various drugs are readily available and known, the substances most frequently used by university students are coffee, cola nuts, alcohol, spirits and cigarettes. Diazepam and diazepoxide are also used with some frequency. Students tend to use stimulants and depressants sequentially, mainly during and after sessional examinations. The stimulants keep them alert while they are studying for an examination, and the depressants help them to rest after an examination is over. Cannabis is well-known and has been tried by many students.

  14. Análise do significado do tempo de imobilidade em modelos experimentais de natação Analysis of the meaning of the immobility time in swimming experimental models

    Directory of Open Access Journals (Sweden)

    Caroline Morini Calil

    2002-12-01

    Full Text Available O objetivo do trabalho foi testar a hipótese de que a interpretação do tempo de imobilidade (desamparo aprendido ou adaptação pode variar conforme o modelo utilizado (teste da natação forçada ou estresse por natação. Foram analisados o tempo de imobilidade (TI e a mobilização de glicogênio de ratos submetidos à natação em dois protocolos: estresse por natação (EN e teste da natação forçada (TNF. Também comparamos os efeitos da desipramina e diazepam. Os experimentos foram filmados para análise do TI. Os ratos, após a sessão de natação, foram sacrificados e amostras do fígado e músculos foram preparadas para quantificação do glicogênio. O TI foi menor no EN comparado ao TNF (p=0,001. As concentrações de glicogênio hepático dos grupos foram diferentes entre si (controle>EN>TNF; pThe aim of this work was to evaluate if the meaning of immobility (helplessness or adaptation depends on the experimental model (forced swimming test or swimming stress. Immobility time (IT and glycogen mobilization of rats submitted to swimming session were analyzed in two protocols: swimming stress (SS and forced swimming test (FST. We also compared the effects of desipramine and diazepam. The experiments were recorded to evaluate the IT. The rats, after swimming session, were sacrificed and hepatic and muscles samples were prepared to the quantification of glycogen. IT was lower in SS than in FST (p=0.001. Hepatic glycogen concentration were different one from another (control>FST>SS;p<0.05. The glycogen concentrations at gastrocnemius and soleus muscles were lower at SS compared to FST and control (p<0.05. The IT was recorded and measured from another group treated with desipramine and diazepam. Desipramine decreased the IT in the FST but not in the SS. Diazepam increased the IT in the SS but not in the FST. We conclude that SS and FST induced different physiological and behavioral responses and represent different situations for the

  15. Magnesium deficiency induces anxiety-and depression-like behavior and metabolic dysfunction in C57Bl/6J mice

    DEFF Research Database (Denmark)

    Winther, G.; Wang, T.; Singewald, N.

    2012-01-01

    ) in mice through depression-and anxiety phenotyping experiments, namely the forced swim test and light-dark box respectively. We determined the behavioural effects 30 minutes after treatment with imipramine (20 mg/kg), diazepam (2 mg/kg) and ketamine (3 mg/kg). The glucose tolerance test was used to assess...... metabolic function in Mg deficient mice. Results: We found that, compared to control (n=10), mice receiving Mg deficient diet (n=10) (10 % RDA), were more immobile in the forced swim test....

  16. Anestesia em eqüinos com síndrome cólica: análise de 48 casos e revisão de literatura Anesthesia in horses with colic syndrome: analysis of 48 cases and literature review

    Directory of Open Access Journals (Sweden)

    Alonso Gabriel Pereira Guedes

    2002-06-01

    Full Text Available A cólica eqüina é uma síndrome que cursa com dor abdominal, distúrbios hidroeletrolíticos e ácido-base e disfunção de órgãos vitais como pulmões e coração. Os procedimentos anestésicos nesses animais apresentam particularidades que aumentam o risco de complicações. Os animais devem ser avaliados no período pré-anestésico e as terapias de reposição devem ser instituídas quando necessárias. A medicação pré-anestésica deve proporcionar analgesia e sedação do animal. A xilazina e/ou butorfanol podem ser utilizados com esse objetivo. A indução pode ser realizada com éter gliceril guaiacolato e cetamina com ou sem diazepam, ou mesmo com cetamina e diazepam pela via intravenosa. A manutenção anestésica deve ser feita preferencialmente com isofluorano, mas o halotano também pode ser utilizado. Manter ventilação pulmonar mecânica, com o animal recebendo oxigênio a 100% durante todo o período cirúrgico e pós-operatório imediato. A recuperação deve ser feita em ambiente escurecido e calmo, com forração e piso não escorregadio. Analgesia e oxigenoterapia também são importantes nessa fase.The equine colic is a syndrome that leads to abdominal pain, hydroeletrolitic and acid-base disturbances and functional alterations of the vital organs like lungs and heart. Anesthetic procedures in these animals show certain particularities that elevate the complications risk. The animals should be evaluated at the preanesthetic period and the reposition treatments should be done as necessary. The premeds should give analgesia and sedation to the animal. Xylazina and/or butorphanol may be used to this aim. Induction can be done with guaiacol glycerine ether, ketamine with/without diazepam, or even with ketamine and diazepam by the intravenous route. Isoflurane is the anesthetic of choice for the maintenance of the anesthesia, but halothane also can be used. Intermitent positive pressure ventilation should be established

  17. Dynamic changes in spectral and spatial signatures of high frequency oscillations in rat hippocampi during epileptogenesis in acute and chronic stages

    Directory of Open Access Journals (Sweden)

    Pan-Pan Song

    2016-11-01

    Full Text Available Objective: To analyze spectral and spatial signatures of high frequency oscillations (HFOs, which include ripples and fast ripples (FRs, > 200 Hz by quantitatively assessing average and peak spectral power in a rat model of different stages of epileptogenesis.Methods: The lithium–pilocarpine model of temporal lobe epilepsy was used. The acute phase of epilepsy was assessed by recording intracranial electroencephalography (EEG activity for 1 day after status epilepticus (SE. The chronic phase of epilepsy, including spontaneous recurrent seizures (SRSs, was assessed by recording EEG activity for 28 days after SE. Average and peak spectral power of five frequency bands of EEG signals in CA1, CA3 and DG regions of the hippocampus were analyzed with wavelet and digital filter.Results: FRs occurred in the hippocampus in the animal model. Significant dynamic changes in the spectral power of FRS were identified in CA1 and CA3. The average spectral power of ripples increased at 20 min before SE (p < 0.05, peaked at 10 min before diazepam injection. It decreased at 10 min after diazepam (p < 0.05 and returned to baseline after 1 hour (h. The average spectral power of FRs increased at 30 min before SE (p < 0.05 and peaked at 10 min before diazepam. It decreased at 10 min after diazepam (p < 0.05 and returned to baseline at 2 h after injection. The dynamic changes were similar between average and peak spectral power of FRs. Average and peak spectral power of both ripples and FRs in the chronic phase showed a gradual downward trend compared with normal rats 14 days after SE.Significance: The spectral power of HFOs may be utilized to distinguish between normal and pathologic HFOs. Ictal average and peak spectral power of FRs were two parameters for predicting acute epileptic seizures, which could be used as a new quantitative biomarker and early warning marker of seizure. Changes in interictal HFOs power in the hippocampus at the chronic stage may be not

  18. Screening of pharmacologic adulterant classes in herbal formulations using voltammetry of microparticles.

    Science.gov (United States)

    Doménech-Carbó, Antonio; Martini, Mariele; de Carvalho, Leandro Machado; Viana, Carine; Doménech-Carbó, María Teresa; Silva, Miguel

    2013-02-23

    A solid state electrochemical method for screening different families of adulterant chemicals illegally added to commercial phytotherapuetic formulations is described. The proposed method, based on the voltammetry of microparticles approach, permits a fast and sensitive way to distinguish between anorexics (amfepramone, fenproporex, sibutramine), benzozodiazepinic anxiolytics (clonazepam, flurazepam, alprazolam, midazolam, medazepam, chlordiazepoxide, diazepam), antidepressants (bupropione, fluoxetine, sertraline, paroxetine), diuretics (hydrochlorothiazide, furosemide, chlortalidone, amiloride, spironolactone), and hypoglycemics (glimepiride, chlorpropamide, glibenclamide) based on characteristic voltammetric signals recorded on solid micro- or nanosamples attached to graphite electrodes immersed into aqueous electrolytes. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Esophageal dilatation using the Eder Puestow dilators.

    Science.gov (United States)

    Royston, C M; Dowling, B L; Gear, M W

    1976-06-01

    We have performed fifty-one dilatations in twenty-six patients using an end-viewing fiberoptic endoscope and Eder Puestow dilators. All (except two) were performed using intravenous diazepam, the majority on an outpatient basis. The only complication has been a single case of aspiration pneumonia. We have found this method of esophageal dilatation particularly useful in the preoperative dilatation of benign strictures, and in those elderly frail patients who are unsuitable for surgery. Transthoracic resection of the stricture is avoided and thus transabdominal repair of the hiatus hernia may be undertaken.

  20. Albumin binding of anti-inflammatory drugs. Utility of a site-oriented versus a stoichiometric analysis

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R

    1984-01-01

    Binding equilibria of 12 nonsteroidal, anti-inflammatory substances, salicylic acid, diflunisal, phenylbutazone, azapropazone, fenbufen, biphenylacetic acid, naproxen, flurbiprofen, ibuprofin, diclofenac, indomethacin, and benoxaprofen, to defatted human serum albumin has been investigated at 37...... degrees, pH 7.4, in a sodium phosphate buffer, 66 mM, by means of equilibrium dialysis and, in case of salicylic acid, by dialysis rate determinations. Cobinding of each of these drugs with monoacetyl-4,4'-diaminodiphenyl sulfone, warfarin, and diazepam has been studied by measuring dialysis rates...

  1. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound...

  2. Évaluation d'une forme galénique à base d'alpha cyclodextrine et d'huile végétale pour l'administration par voie orale de molécules actives peu solubles dans l'eau

    OpenAIRE

    Hamoudi , Mounira Chérifa

    2012-01-01

    The general aim of this thesis was the study of the potential of beads, made of α-cyclodextrin and soybean oil, for the oral delivery of poorly water soluble drugs. We have first verified that it was possible to encapsulate in beads, active molecules (progesterone and indomethacin), other than retinoid and diazepam, with a high drug loading and a satisfying yied. The study of the behaviour of freeze-dried naked beads, in terms of stability and drug release in simulated gastro-intestinal fluid...

  3. [3H]muscimol binding sites increased in autopsied brains of chronic schizophrenics

    International Nuclear Information System (INIS)

    Hanada, S.; Mita, T.; Nishino, N.; Tanaka, C.

    1987-01-01

    [ 3 H]muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and 17 control subjects were investigated. In the schizophrenics, saturation analysis with varying concentrations of [ 3 H]muscimol revealed an increase in the number GABA/sub A/ receptors, but there was no significant difference in the affinity. In addition, the enhancement of [ 3 H]muscimol binding by diazepam was significantly greater in schizophrenics than in controls. GAD activity did not differ between controls and schizophrenics. The possibility that GABAergic mechanisms might play a role in case of chronic schizophrenia should be given further attention

  4. De fleste anæstesimidler kan bruges uden skadelig påvirkning af barnet ved amning

    DEFF Research Database (Denmark)

    Sønderskov, Michèle Lefort; Albrechtsen, Charlotte Krebs; Bille, Anders Bastholm

    2011-01-01

    physicians. However, individual drugs such as diazepam, morphine, codeine and pethidine should be avoided when possible and otherwise only be administered as single doses with observation of the child. There is an urgent need for high-quality research before sufficient light can be shed on this topic.......Breastfeeding women who undergo general anaesthesia often receive conflicting recommendations regarding the need to discard their milk before resumption of breastfeeding. This narrative review describes the sparse evidence to support the current practice of discarding milk as advocated by many...

  5. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

    International Nuclear Information System (INIS)

    Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

    2012-01-01

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA A receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death.

  6. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu [Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, 10595 (United States); Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Velíšková, Jana [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Stanton, Patric K., E-mail: patric_stanton@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Velíšek, Libor [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Department of Pediatrics, New York Medical College, Valhalla, NY 10595 (United States)

    2012-11-15

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death

  7. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

    Science.gov (United States)

    Shinnar, Shlomo; Gloss, David; Alldredge, Brian; Arya, Ravindra; Bainbridge, Jacquelyn; Bare, Mary; Bleck, Thomas; Dodson, W. Edwin; Garrity, Lisa; Jagoda, Andy; Lowenstein, Daniel; Pellock, John; Riviello, James; Sloan, Edward; Treiman, David M.

    2016-01-01

    CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events

  8. Electrocardiographic and hemato-biochemical effects of two balanced anesthetic protocols in dogs

    Directory of Open Access Journals (Sweden)

    Anubhav Khurana

    2014-10-01

    Full Text Available Aim: The purpose of this study was to compare the electrocardiographic (ECG, hematological and clinico-biochemical effects of two balanced anesthetic protocols in dogs. Materials and Methods: A total of 20 clinical cases of dogs, randomly divided into two groups of 10 animals each were made part of study. All dogs were premedicated with injection atropine sulfate @ 0.04 mg/kg body weight (b. wt. subcutaneously followed 15 min later with injection butorphanol tartarate @ 0.2 mg/kg b. wt. intravenous (IV. Subsequently after 10 min premedicated with injection diazepam @ 0.5 mg/kg b. wt. IV (Group DP or injection acepromazine maleate @ 0.015 mg/kg b. wt. IV (Group AP followed by injection propofol “till effect” IV for induction of surgical anesthesia. The animals were immediately transferred to halothane in oxygen. Observations recorded in dogs included ECG recordings, hematological and clinico-biochemical observations at various time intervals. Results: No arrhythmia was observed in any animal pre-operatively and intra-operatively in any of the groups. Significant fall in packed cell volume (PCV and total erythrocyte count occurred in DP group in early phase, whereas only PCV decreased significantly in AP group. Biochemical parameters were non-significant in both the groups. Conclusion: Both diazepam-butorphanol-propofol-halothane and acepromazine-butorphanol-propofol-halothane are safe with respect to their ECG, hematological and biochemical effects in clinical cases.

  9. Peripheral-type benzodiazepine receptor: a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands

    International Nuclear Information System (INIS)

    Snyder, S.H.; Verma, A.; Trifiletti, R.R.

    1987-01-01

    The peripheral-type benzodiazepine receptor is a site identified by its nanomolar affinity for [ 3 H]diazepam, similar to the affinity of diazepam for the central-type benzodiazepine receptor in the brain. The peripheral type benzodiazepine receptor occurs in many peripheral tissues but has discrete localizations as indicated by autoradiographic studies showing uniquely high densities of the receptors in the adrenal cortex and in Leydig cells of the testes. Subcellular localization studies reveal a selective association of the receptors with the outer membrane of mitochondria. Photoaffinity labeling of the mitochondrial receptor with [ 3 H]flunitrazepam reveals two discrete labeled protein bands of 30 and 35 kDa, respectively. The 35-kDa band appears to be identical with the voltage-dependent anion channel protein porin. Fractionation of numerous peripheral tissues reveals a single principal endogenous ligand for the receptor, consisting of porphyrins, which display nanomolar affinity. Interactions of porphyrins with the mitochondrial receptor may clarify its physiological role and account for many pharmacological actions of benzodiazepines

  10. Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions

    International Nuclear Information System (INIS)

    Fernandez-Fontaina, E.; Gomes, I.B.; Aga, D.S.; Omil, F.; Lema, J.M.; Carballa, M.

    2016-01-01

    The effect of nitrification, nitratation and heterotrophic conditions on the biotransformation of several pharmaceuticals in a highly enriched nitrifying activated sludge was evaluated in this study by selective activation of ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and heterotrophic bacteria. Nitrifiers displayed a noticeable capacity to process ibuprofen due to hydroxylation by ammonia monooxygenase (AMO) to produce 2-hydroxy-ibuprofen. Naproxen was also biotransformed under nitrifying conditions. On the other hand, heterotrophic bacteria present in the nitrifying activated sludge (NAS) biotransformed sulfamethoxazole. In contrast, both nitrifying and heterotrophic activities were ineffective against diclofenac, diazepam, carbamazepine and trimethoprim. Similar biotransformation rates of erythromycin, roxithromycin and fluoxetine were observed under all conditions tested. Overall, results from this study give more evidence on the role of the different microbial communities present in activated sludge reactors on the biological removal of pharmaceuticals. - Highlights: • The removal of pharmaceuticals in nitrifying activated sludge (NAS) was studied. • Nitrifying activity increases biotransformation rate of ibuprofen and naproxen. • Hydroxylation of ibuprofen by ammonia monooxygenase of ammonia oxidizing bacteria • Heterotrophic activity enhances biotransformation of sulfamethoxazole in NAS. • Recalcitrance of trimethoprim, diclofenac, carbamazepine and diazepam in NAS

  11. Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice.

    Science.gov (United States)

    Rizzi, A; Vergura, R; Marzola, G; Ruzza, C; Guerrini, R; Salvadori, S; Regoli, D; Calo, G

    2008-05-01

    Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice. Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice. NPS (0.01-1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5 mg kg(-1)). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15 mg kg(-1)) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively. We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.

  12. Psychopharmacological properties of saponins from Randia nilotica stem bark.

    Science.gov (United States)

    Danjuma, N M; Chindo, B A; Abdu-Aguye, I; Anuka, J A; Hussaini, I M

    2014-01-01

    Decoctions of Randia nilotica Stapf. (Rubiaceae) have been used in the Nigerian traditional medicine for the management of epilepsy, anxiety, depression and psychosis for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. The aim of this study is to establish whether the saponins present in R. nilotica are responsible for its acclaimed beneficial effects in Nigerian traditional medicine. The behavioural properties of the saponin-rich fraction (SFRN) of R. nilotica stem bark were studied on hole-board, diazepam-induced sleep, rota-rod and beam-walking in mice. The anticonvulsant properties of SFRN were also examined on maximal electroshock, pentylenetetrazole- and strychnine-induced seizures in mice. The intraperitoneal LD₅₀ of SFRN in mice and rats were estimated to be 11.1 and 70.7 mg/kg, respectively. SFRN significantly prolonged the duration of diazepam-induced sleep; diminished head dip counts in the hole-board test and protected mice against maximal electroshock seizures. SFRN failed to protect mice against pentylenetetrazole- and strychnine-induced seizures; and had no effect on motor coordination on the rota-rod treadmill at the doses tested. SFRN significantly decreased the number of foot slips in the beam-walking assay in mice with no effect on time to reach the goal box. This study provides evidence of the psychopharmacological effects of SFRN, thus supporting further development of the psychoactive components as remedies for epilepsy.

  13. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines.

    Science.gov (United States)

    Stanley, Joanna L; Lincoln, Rachael J; Brown, Terry A; McDonald, Louise M; Dawson, Gerard R; Reynolds, David S

    2005-05-01

    The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.

  14. The effect of Quinpirol and Sulpiride on the brain activity waves in conscious and aneasthetized rat

    Directory of Open Access Journals (Sweden)

    Komaki AR

    1998-06-01

    Full Text Available Brain's waves are produced by spontaneous activity of neurons. These waves are changed by neurotransmitters in the central nervous system (CNS. Concentration of these neurotransmitters can be changed by various drugs and total power of brain waves also increase or decrease by these drugs. In this research effect of Quinpirol and Sulpiride on the brain waves was investigated. Male wistar rats (weight 190-230 were aneasthetized with thiopental and two holes were made into the frontal and occipital area and two Ag/AgCl electrodes were fixed into these holes. One week after recovery, two electrodes were connected to the physiograph and the results were analyzed before and after intraperitoneal and intracerebroventricular (ICV injection of drugs by PC computer. Our results showed that intraperitoneal administration (5 mg/kg of diazepam reduced the depth of anesthesia. Conversely, intracerebroventricular injection of sulpiride increased the depth of anesthesia which was manifested by an increase in relative power of delta waves and reduction of relative power of alpha waves. This drug had a biphasic effect on EEG, at high doses in increased the depth of aneasthesia and total sleep. Wehteas depth of anesthesia was decreased at low dose. Simutanuos administration of sulpiride and quinpirole produced an effect on EEG similar to diazepam. As a result, biphasic effect of D2 agonist and antagonist drugs on brain waves are due to nonspecific action of these drugs on these receptors and this effect may be produced by other mechanisms

  15. Influence of benzodiazepines on body weight and food intake in obese and lean Zucker rats.

    Science.gov (United States)

    Blasi, C

    2000-05-01

    1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered in obese (fa/fa) Zucker rats, plays an important role in controlling energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms in these animals due to a genetically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam) lowered insulin concentration in obese rats. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clarify the pathophysiology of obesity and insulin resistance in fatty Zucker rats.

  16. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    International Nuclear Information System (INIS)

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T.

    1991-01-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain

  17. Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia.

    Science.gov (United States)

    Seillier, Alexandre; Giuffrida, Andrea

    2017-10-01

    Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.

  18. Burning Mouth Syndrome pada wanita Menopause dengan Hiposalivasi, Coated Tongue dan Gangguan Pengecapan serta Penatalaksanaannya

    Directory of Open Access Journals (Sweden)

    Sri Hadiati

    2012-06-01

    Full Text Available Blackground: Burning mouth syndrome (BMS is a disorder that is characterized by a burning sensation of the oral cavity in the absence of visible local or systemic abnormalities. Affected patient often present with multiple oral complaints, including burning, dryness and taste alterations. The exact cause of burning mouth syndrome often is difficult to pin point. Conditions that have been reported in association with burning mouth syndrome include menopause, hyposlivation, coated tongue, taste alterations and psychologic condition. Objective: To report a case of burning mouth syndrome in postmenopausal women with hyposalivation, coated tongue, taste alterations and psychologic condition and its management. Case and management: a case of burning mouth syndrome in women with menopause, hyposalivation, coated tongue, and taste alterations, was managed effectively by gabapentin 100mg, probiotic chewing gum, diazepam 2mg and vitamin B1, B6, B12. Conclusion: Oral burning appears to be most prevalent in postmenopausal women often present with multiple oral complaints, including burning, dryness and taste alterations, in this case was managed effectively by gabapentin 100mg, prebiotic chewing gum, diazepam 2mg and vitamin B1, B6, B12.

  19. Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

    Science.gov (United States)

    Joshi, Hanumanthachar; Parle, Milind

    2006-02-01

    Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

  20. Evaluation of antibacterial, antioxidant and nootropic activities of Tiliacora racemosa Colebr. leaves: In vitro and in vivo approach.

    Science.gov (United States)

    T, Vivek Kumar; M, Vishalakshi; M, Gangaraju; Das, Parijat; Roy, Pratiti; Banerjee, Anindita; Dutta Gupta, Sayan

    2017-02-01

    The antibacterial and antioxidant potential of Tiliacora racemosa leaf extracts in various solvents (methanolic, hexane, chloroform and ethyl acetate) was determined. Additionally, the presence of bisbenzylisoquinoline alkaloids in the plant prompted us to evaluate the nootropic activity of the methanolic extract in mice. Further, we seek to verify the nootropic effect by examining the anticholinesterase inhibition potential of the methanolic extract. The leaf extracts in various solvents were evaluated for their antibacterial and antioxidant activity by agar diffusion technique and α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method, respectively. The ex vivo acetylcholine esterase inhibitory activity of the methanolic extract was carried out by Ellman's method in male Wistar rats. The nootropic capacity of the methanolic extract was examined in Swiss albino mice by utilizing the diazepam induced acute amnesic model. The chloroform/n-hexane and ethyl acetate fraction showed promising antioxidant and antibacterial (Gram positive and Gram negative bacteria) property, respectively. The methanolic extract was able to diminish the amnesic effect induced by diazepam (1mg/kg i.p.) in mice. The extract also showed significant acetyl cholinesterase inhibition in rats. The findings prove that the memory enhancing capability is due to increased acetyl choline level at the nerve endings. The strong antioxidant nature and potential nootropic activity shown by the extract suggests its future usage in the treatment of neurodegenerative disorders such as dementia and Alzheimer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants.

    Science.gov (United States)

    Moreau, J. L.; Pieri, L.; Prud'hon, B.

    1989-01-01

    1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA-induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors. PMID:2574061

  2. Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology.

    Science.gov (United States)

    Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas

    2005-05-15

    This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.

  3. Pharmacology of midazolam.

    Science.gov (United States)

    Pieri, L; Schaffner, R; Scherschlicht, R; Polc, P; Sepinwall, J; Davidson, A; Möhler, H; Cumin, R; Da Prada, M; Burkard, W P; Keller, H H; Müller, R K; Gerold, M; Pieri, M; Cook, L; Haefely, W

    1981-01-01

    8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam. It produces all the characteristic effects of the benzodiazepine class, i.e., anticonvulsant, anxiolytic, sleep-inducing, muscle relaxant, and "sedative" effects. The magnitude of the anticonflict effect of midazolam is smaller than that of diazepam in rats and squirrel monkeys, probably because a more pronounced sedative component interferes with the increase of punished responses. In rodents, surgical anaesthesia is not attained with midazolam alone even in high i.v. doses, whereas this state is obtained in monkeys. The drug potentiates the effect of various central depressant agents. Midazolam is virtually free of effects on the cardiovascular system in conscious animals and produces only slight decreases in cardiac performance in dogs anaesthetized with barbiturates. No direct effects of the drugs on autonomic functions were found, however, stress-induced autonomic disturbances are prevented, probably by an effect on central regulatory systems. All animal data suggest the usefulness of midazolam as a sleep-inducer and i.v. anaesthetic of rapid onset and short duration.

  4. Degradation of benzodiazepines using water falling film dielectric barrier discharge reactor

    Directory of Open Access Journals (Sweden)

    Radulović Vesna M.

    2017-01-01

    Full Text Available Classical methods of wastewater treatment are often not suitable for the treatment of pharmaceutical waste. The previous studies have shown that the use of the advanced oxidation procedures (AOP can lead to a more efficient degradation of various biologically active compounds, which are active pharmaceutical ingredients of applied drugs. The aim of this paper is the application of the plasma technology on the degradation of a two active pharmaceutical ingredients (APIs, diazepam and alprazolam and the finished products (Bensedin® and Ksalol® using the dielectric barrier discharge (DBD reactor for AOP. We studied the degradation rate of these pharmaceuticals, depending on the number of passes through the reactor. This degradation method was efficient 61 % for diazepam and 95 % alprazolam. We also examined the influence of the pH adjustment between the passes of APIs through the DBD reactor. The degradation rate of APIs and the finished products was monitored by the high performance liquid chromatography (HPLC technique, using a photodiode array detector. The concentration of the dissolved ozone was determined using the iodometric procedure. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172030

  5. Effect ofPunica granatum peel extract on learning and memory in rats

    Institute of Scientific and Technical Information of China (English)

    Shalini Adiga; Prabhav Trivedi; Ravichandra V; Debashree Deb; Forum Mehta

    2010-01-01

    Objective:To evaluate potential memory enhancing effect ofPunica granatum peel extract on rats.Methods: Healthy adult male albino rats of Wistar strain were used. Each group of6 rats were administered either distilled water or50mg/kg of extract or100 mg/kg of extract for 15days and subjected to passive avoidance test or T-maze test. In the next phase rats were administered distilled water or100 mg/kg of extract for15 days and the rats were given injection diazepam before subjecting them to the tests.Results:The overall performance was better in test groups compared to control groups. Among the test groups,100 mg/kg rats performed better than50mg/kg. The effect on spatial learning parameters like mean number of alternations and mean percentage bias was more marked compared to retention testing parameters like latency. 100 mg/kg Punica extract treated group also improved performance of diazepam treated rats. Conclusions:There is a definite trend of memory improvement byPunica granatum peel with effects being more marked on spatial learning tendency and long term memory than on retention capacity.

  6. Memory-Enhancing Activity of Palmatine in Mice Using Elevated Plus Maze and Morris Water Maze

    Directory of Open Access Journals (Sweden)

    Dinesh Dhingra

    2012-01-01

    Full Text Available The present study was designed to evaluate the effect of palmatine on memory of Swiss young male albino mice. Palmatine (0.1, 0.5, 1 mg/kg, i.p. and physostigmine (0.1 mg/kg, i.p. per se were administered for 10 successive days to separate groups of mice. Effect of drugs on learning and memory of mice was evaluated using elevated plus maze and Morris water maze. Brain acetylcholinesterase activity was also estimated. Effect of palmatine on scopolamine- and diazepam-induced amnesia was also investigated. Palmatine (0.5 and 1 mg/kg and physostigmine significantly improved learning and memory of mice, as indicated by decrease in transfer latency using elevated plus maze, and decrease in escape latency during training and increase in time spent in target quadrant during retrieval using Morris water maze. The drugs did not show any significant effect on locomotor activity of the mice. Memory-enhancing activity of palmatine (1 mg/kg was comparable to physostigmine. Palmatine (1 mg/kg significantly reversed scopolamine- and diazepam-induced amnesia in mice. Palmatine and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. Thus, palmatine showed memory-enhancing activity in mice probably by inhibiting brain acetylcholinesterase activity, through involvement of GABA-benzodiazepine pathway, and due to its antioxidant activity.

  7. Potential intravenous drug incompatibilities in a pediatric unit.

    Science.gov (United States)

    Leal, Karla Dalliane Batista; Leopoldino, Ramon Weyler Duarte; Martins, Rand Randall; Veríssimo, Lourena Mafra

    2016-01-01

    To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student's t test and ANOVA; the level of significance was set at 5% (ppenicilina G e ceftriaxona. Quase 85% das crianças apresentaram ao menos uma potencial incompatibilidade, razão de 1,2 incompatibilidades/paciente. Os tipos de incompatibilidades mais comuns foram: não testada (93,4%), precipitação (5,5%), turbidez (0,7%) e decomposição química (0,4%). Os fatores associados a potenciais incompatibilidades foram: número de medicamentos e a prescrição dos medicamentos diazepam, fenitoína, fenobarbital e metronidazol. A maioria das prescrições pediátricas apresentou potenciais incompatibilidades e a incompatibilidade não testada foi o tipo mais comum. O número de medicamentos e a prescrição dos medicamentos diazepam, fenobarbital, fenitoína e metronidazol foram fatores de risco para potenciais incompatibilidades.

  8. Preparation and characterization of a self-emulsifying pellet formulation.

    Science.gov (United States)

    Abdalla, Ahmed; Mäder, Karsten

    2007-05-01

    The purpose of the current study is to investigate the feasibility of producing solid self-emulsifying pellets using the extrusion/spheronization technique. Pellets were made from a mixture of C18 partial glycerides, Solutol HS15 and microcrystalline cellulose. Pellets with good physical properties (size, shape, friability) and self-emulsifying properties were produced. The pellets were, in contrast to pellets lacking Solutol, able to transfer a lipophilic dye and a spin probe into the aqueous media. The release kinetics and the microenvironment of the pellets during the release process were assessed using electron spin resonance (ESR) spectroscopy. The ESR results showed that the hydrophobic spin probe was localized mainly in the lipid environment all over the release time. Furthermore, the formulation was capable of accelerating the release of the drug diazepam and achieving a diazepam concentration above its saturation solubility. In conclusion, spherical pellets with low friability and self-emulsifying properties can be produced by the standard extrusion/spheronization technique. The pellets are capable of transfering lipophilic compounds into the aqueous phase and have a high potential to increase the bioavailability of lipophilic drugs.

  9. Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Fontaina, E., E-mail: eduardo.fernandez.fontaina@usc.es [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Gomes, I.B. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Aga, D.S. [Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Omil, F.; Lema, J.M.; Carballa, M. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain)

    2016-01-15

    The effect of nitrification, nitratation and heterotrophic conditions on the biotransformation of several pharmaceuticals in a highly enriched nitrifying activated sludge was evaluated in this study by selective activation of ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and heterotrophic bacteria. Nitrifiers displayed a noticeable capacity to process ibuprofen due to hydroxylation by ammonia monooxygenase (AMO) to produce 2-hydroxy-ibuprofen. Naproxen was also biotransformed under nitrifying conditions. On the other hand, heterotrophic bacteria present in the nitrifying activated sludge (NAS) biotransformed sulfamethoxazole. In contrast, both nitrifying and heterotrophic activities were ineffective against diclofenac, diazepam, carbamazepine and trimethoprim. Similar biotransformation rates of erythromycin, roxithromycin and fluoxetine were observed under all conditions tested. Overall, results from this study give more evidence on the role of the different microbial communities present in activated sludge reactors on the biological removal of pharmaceuticals. - Highlights: • The removal of pharmaceuticals in nitrifying activated sludge (NAS) was studied. • Nitrifying activity increases biotransformation rate of ibuprofen and naproxen. • Hydroxylation of ibuprofen by ammonia monooxygenase of ammonia oxidizing bacteria • Heterotrophic activity enhances biotransformation of sulfamethoxazole in NAS. • Recalcitrance of trimethoprim, diclofenac, carbamazepine and diazepam in NAS.

  10. Identification of Molecular Substrate for the Attenuation of Anxiety: A Step Toward the Development of Better Anti-Anxiety Drugs

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    Uwe Rudolph

    2001-01-01

    Full Text Available Anxiety disorders affect some 19 million people in the U.S. alone, costing $46.6 billion, or one third of the nation’s total mental health bill in 1990. Benzodiazepine tranquilizers like the prototypic diazepam are among the most widely used anti-anxiety agents. In addition to their anxiolytic action, they also induce sedation and may impair motor coordination, both of which are undesired side effects when they are used as anxiolytics. Not surprisingly, road traffic accidents may be increased for patients on classical benzodiazepines. In addition, these drugs carry the risk of dependence liability. Benzodiazepines augment the action of the inhibitory neurotransmitter g-aminobutyric acid (GABA at contact points between two nerve cells called synapses, points at which information is transmitted from one nerve cell to the next. Synaptically released GABA binds to postsynaptic GABAA receptors, thus causing an influx of negatively charged chloride ions into the postsynaptic neuron. This leads to a hyperpolarization and thus functional inhibition of the postsynaptic cell. Benzodiazepines bind to a site on the GABAA receptor which is different from the GABA binding site, thus increasing the chloride current. Benzodiazepines like diazepam bind to GABAA receptors containing the α subunits α1, α2, α3, or α5, most likely in abgabg combinations.

  11. Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

    Science.gov (United States)

    Melo, Francisca Helvira Cavalcante; Venâncio, Edith Teles; de Sousa, Damião Pergentino; de França Fonteles, Marta Maria; de Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro Barros; de Sousa, Francisca Cléa Florenço

    2010-08-01

    Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate-induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open-field test. However, CVC decreased the number of groomings in the open-field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate-induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open-field test.

  12. Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice.

    Science.gov (United States)

    Ene, Hila M; Kara, Nirit Z; Barak, Noa; Reshef Ben-Mordechai, Tal; Einat, Haim

    2016-04-01

    A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs' affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice. Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery. The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity. The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.

  13. Nonconvulsive status epilepticus due to ifosfamide.

    Science.gov (United States)

    Kilickap, Saadettin; Cakar, Mustafa; Onal, Ibrahim K; Tufan, Abdurrahman; Akoglu, Hadim; Aksoy, Sercan; Erman, Mustafa; Tekuzman, Gulten

    2006-02-01

    To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

  14. Anticonvulsant potentials of ethanolic extract of Eleusine indica

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    Ette Okon Ettebong

    2016-11-01

    Full Text Available Objective: To assess the anticonvulsant potentials of ethanolic extract of Eleusine indica. Methods: Albino Wistar mice were separated into five groups with six animals in each group and thereafter pretreated with distilled water, various doses of the extract (200–600 mg/kg and standard drug diazepam (0.5 mg/kg. Thirty minutes later, pentylenetetrazole (70 mg/kg, aminophylline (280 mg/kg and isoniazid (250 mg/kg were used to induce convulsions by intraperitoneal administration. These mice were then placed in plexiglas cages and monitored for the occurrence of seizures over a thirty-minute time period. The latency of convulsions, duration of tonic convulsions and mortality protection were recorded. Data obtained were analyzed using GraphPad InStat 3.10. Results: The results showed that the extract exhibited a dose-dependent increase in the latency of clonic convulsions and decrease in duration of tonic convulsions as compared to the control and these effects were statistically significant (P < 0.001. The extract also provided protection against the mortality which was similar to that produced by the standard drug diazepam. Conclusions: The significant increase in the latency of clonic convulsions and decrease in duration of tonic convulsions caused by the extract show anticonvulsant activity and corroborate with the claims of the traditional use of the plant as an anticonvulsant remedy.

  15. STRUCTURAL AND FUNCTIONAL ASPECTS OF ACYL-COENZYME A BINDING PROTEINS (ACBPs: A COMPREHENSIVE REVIEW

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    Richa Arya

    2012-06-01

    Full Text Available ACBP was originally identified as a mammalian diazepam binding inhibitor – a neuropeptide that has the ability to inhibit diazepam binding to the �-aminobutyric acid (GABA receptor (Guidotti et al., 1983. Typically, ACBPs are small (~10 kDa cytosolic proteins (Burton et al., 2005. However, a number of hybrid ACBPs are reported that are fused with ankyrin repeats, such as ACBP1 and ACBP2 in Arabidopsis thaliana (Chye et al., 1999; Li and Chye, 2003. Other functional domains, such as the human peroxisomal �3/ �2-enoyl-CoA isomerase (Geisbrecht et al., 1999, or any non-functional/ uncharacterized domain are also cited. ACBP predominantly functions as an intracellular acyl-CoA transporter and pool former, and is critical to lipid metabolism in cells (Gossett et al., 1996; Knudsen et al., 2000; Schroeder et al., 1998. Impaired lipid metabolism and other cellular functions in humans arising out of ACBP defects thus need to be explored. ACBP has only been reported in eukaryotes, not in prokaryotes, except for a few pathogenic eubacteria that might have acquired ACBP from eukaryotic hosts via lateral gene transfer (Burton et al., 2005. Whole genome sequences of several prokaryotes and pathogens being available currently, it is worthwhile to extend search for ACBPs beyond eukaryotes as well, to explore their potential as drug targets, given their essential role in lipid metabolism. As a prelude to such investigations, the current review summarizes available knowledge of ACBPs and outlines the scope of future research.

  16. [Modification of the analgetic effects (buprenorphine, pentazocine, pethidine) on respiration and haemodynamics by epidural, halothane- or neuroleptanaesthesia (author's transl)].

    Science.gov (United States)

    Wüst, H J; Moritz, K G; Sandmann, W; Richter, O

    1980-04-01

    In 38 patients buprenorphine, meperidine and pentazocine were given in a single dose for postoperative pain relief 20 hours after the end of anaesthesia. Measuring the parameters of the high- and low-pressure system as well as the metabolism the authors found that the effects of these analgetic medicaments, intravenously injected were significantly influenced by fentanyl, halothane or diazepam, given under the course of operation. Especially buprenorphine, injected after epidural anaesthesia in combination with diazepam sedation, proved to have a rather negative effect, because it caused a strong depression of respiration and circulation. On the other hand buprenorphine had, given after neuroleptanaesthesia, a neutralizing - and pentazocine and pethidine in combination with neuroleptanaesthesia a stimulating influence on the circulation. After halothane-anaesthesia the effect of the analegtics on the cardiovascular system was, when buprenorphine was given, depressing and when pentazocine was given indifferent. Similar reactions, but more pronounced, could be seen in the epidural group. With certain reservations, caused by the preliminary character of this study, the following conclusions can be drawn for the anaesthetic practice: 1 Choosing analgetic drugs for postoperative pain relief, the anaesthesist has to be aware of the interactions, possibly resulting from the medicaments, given during anaesthesia. 2. The number of medicaments, given during anaesthesia, should be kept small, considering the eventual interactions and the unintentional secondary effects.

  17. Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1981-03-26

    Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.

  18. Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

    Science.gov (United States)

    Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

    2018-08-01

    Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Management protocols for status epilepticus in the pediatric emergency room: systematic review article

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    Cheuk C. Au

    Full Text Available Abstract Objective: This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department treatment of status epilepticus. Sources: Systematic search of national or regional guidelines (January 2000 to February 2017 contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. Summary of findings: 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 emergency department guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11 guidelines recommended phenytoin, but other options were phenobarbital (nine/11, valproic acid (six/11, and either fosphenytoin or levetiracetam (each four/11; third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital. Conclusions: All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery.

  20. Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

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    I. Izquierdo

    1991-01-01

    Full Text Available In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB, an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.

  1. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

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    Pavel Gershokovich

    2015-08-01

    Full Text Available Purpose: Benzodiazepines (BDZs are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS. Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored.

  2. Evaluation of anticonvulsant and neuroprotective effects of camel milk in strychnine-induced seizure model

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    Humera Khatoon

    2015-10-01

    Full Text Available Objective: To discover the use of camel milk as an alternate medicine for the treatment and prevention of convulsions using strychnine-induced seizure model. Methods: Thirty animals were divided into three equal groups. Group I was on distilled water, Group II was on camel milk for 15 days prior to experiment and Group III was on reference drug diazepam. On the day of experiment, strychnine was administered in all treatment groups after distilled water, camel milk and diazepam treatments respectively. Animals were observed for 30 min for latency of seizure onset, frequency of convulsions and duration of jerks. The mortality rate was also evaluated for each group. Results: Camel milk treatment showed significant seizure protection as observed by delayed seizure onset (P ≤ 0.001, decreased total duration of convulsions (P ≤ 0.001 and mortality rate (P ≤ 0.001 when compared with Group I. Conclusions: Anticonvulsant activity of camel milk could be due to potentiation of glycinergic and GABAergic activities both. Antioxidant activity can also amplify its antiepileptic activity. Further studies are required to confirm the exact mechanism of action.

  3. Behavioural profiles in the mouse defence test battery suggest anxiolytic potential of 5-HT(1A) receptor antagonists.

    Science.gov (United States)

    Griebel, G; Rodgers, R J; Perrault, G; Sanger, D J

    1999-05-01

    Compounds varying in selectivity as 5-HT1A receptor antagonists have recently been reported to produce anxiolytic-like effects comparable to those of benzodiazepines in the mouse elevated plus-maze procedure. In view of the potential clinical significance of these findings, the present experiments compared the behavioural effects of diazepam (0.5-3.0 mg/kg) with those of several non-selective 5-HT1A receptor antagonists [NAN-190, 0.1-3.0 mg/kg, MM-77, 0.03-1.0 mg/kg, (S)-UH-301, 0.3-3.0 mg/kg and pindobind-5-HT1A, 0.03-1.0 mg/kg], and three selective 5-HT1A receptor antagonists (WAY100635, 0.01-3.0 mg/kg, p-MPPI, 0.1-3.0 mg/kg and SL88.0338, 0.3-3.0 mg/kg) in the mouse defence test battery (MDTB). In this well-validated anxiolytic screening test, Swiss mice are directly confronted with a natural threat (a rat) as well as situations associated with this threat. Primary measures taken during and after rat confrontation were flight, risk assessment (RA), defensive threat/attack and escape attempts. Diazepam significantly decreased flight reactions after the rat was introduced into the runway, reduced RA activities of mice chased by the rat, increased RA responses displayed when subjects were constrained in a straight alley and reduced defensive upright postures and biting upon forced contact. All the selective 5-HT1A receptor antagonists and NAN-190 also reduced flight, RA in the chase test, and defensive threat and attack behaviours. (S)-UH-301 and pindobind-5-HT1A reduced RA in the chase test, but only partially modified defensive threat and attack. Unlike the other drugs tested, MM-77 produced significant effects only at doses which also markedly reduced spontaneous locomotor activity, suggesting a behaviourally non-specific action. In contrast to diazepam, the 5-HT1A receptor ligands failed to affect RA in the straight alley test. Following removal of the rat from the test area, only diazepam and (S)-UH-301 reduced escape behaviour (contextual defence) at doses

  4. Acute orexigenic effect of agmatine involves interaction between central α2-adrenergic and GABAergic receptors.

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    Taksande, Brijesh Gulabrao; Sharma, Omi; Aglawe, Manish Manohar; Kale, Mayur Bhimrao; Gawande, Dinesh Yugraj; Umekar, Milind Janraoji; Kotagale, Nandkishor Ramdas

    2017-09-01

    Agmatine and GABA have been abundantly expressed in brain nuclei involved in regulation of energy homeostasis and promoting stimulation of food intake in rodents. However, their mutual interaction, if any, in the elicitation of feeding behavior is largely remains unclear. The current study provides experimental evidence for the possible interaction of agmatine, adrenergic and GABAergic systems in stimulation of feeding in satiated rats. Satiated rats fitted with intracerebroventricular (i.c.v.) cannulae and were administered agmatine, alone or jointly with (a) GABA A receptor agonist, muscimol, diazepam or antagonist bicuculline and flumazenil, GABA A positive modulator, allopregnanolone or negative modulator of GABA A receptor, dehydroepiandrosterone (b) In view of the high affinity of agmatine for α 2 -adrenoceptors and the close association between α 2 -adrenoceptors and GABAergic system, the effect of their modulators on feeding elicited by agmatine/GABAergic agonists were also examined. I.c.v. administration of agmatine (40-80μg/rat) induces the significant orexigenic effect in satiated rats. The orexigenic effect of agmatine was potentiated by muscimol (25ng/rat, i.c.v.); diazepam (0.5mg/kg, i.p.); allopregnanolone (0.5mg/kg, s.c.) and blocked by bicuculline (1mg/kg, i.p.) and dehydroepiandrosterone (4mg/kg,s.c.). However, it remained unaffected in presence of flumazenil (25ng/rat, i.c.v.). The orexigenic effect of agmatine and GABAergic agonists was potentiated by a α 2 -adrenoceptors agonist, clonidine (10ng/rat, i.c.v.) and blocked by its antagonist, yohimbine (5μg/rat, i.c.v.). Yohimbine also blocked the hyperphagic effect elicited by ineffective dose combination of agmatine (5μg/rat, i.c.v.) with muscimol (25ng/rat, i.c.v.) or diazepam (0.5mg/kg, i.p.) or allopregnanolone (0.5mg/kg,s.c.). The results of the present study suggest that agmatine induced α 2 -adrenoceptors activation might facilitate GABAergic activity to stimulate food intake in

  5. Evaluating pharmacological models of high and low anxiety in sheep

    Directory of Open Access Journals (Sweden)

    Rebecca E. Doyle

    2015-12-01

    Full Text Available New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenylpiperazine (mCPP; 1 mg/kg; n = 12, an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12, or acted as a control (saline intramuscular injection n = 11. Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a ‘runway task’ (moving down a raceway for a food reward, response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001, a greater startle response (1.4 vs. 0.6; p = 0.02, a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001, and a lower feeding motivation (1.8 × slower; p < 0.001 than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of

  6. Variation of tumour radiosensitivity with time after anaesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Nias, A.H.W.; Perry, P.M. (Saint Thomas' Hospital, London (UK). Richard Dimbleby Research Lab.)

    1989-10-01

    Transplanted C{sub 3}H mouse mammary tumours were given single doses of X irradiation in air or oxygen at 1 atmosphere (atm) with or without anaesthesia of recipient mice by ketamine and diazepam. The radiation response to single doses of 25 Gy was determined in terms of time taken to reach 3.5 times the treatment volume. Under all conditions there was more growth delay in tumours irradiated in pure oxygen than in air. In air and oxygen, the radiation response for anaestheitized animals tended to fall below the level for non-anaesthetized ones when only 10 min had elapsed after administration of anaesthesia. After 25 min, the response in air was back to the level for non-anaesthetized animals but the oxygen group then showed significant sensitization compared with the oxygen without anaesthetic group. After 40 min, the air group showed slight sensitization and the oxygen group still showed significant sensitization by the anaesthetic. (author).

  7. Bergamot Essential Oil Attenuates Anxiety-Like Behaviour in Rats.

    Science.gov (United States)

    Rombolà, Laura; Tridico, Laura; Scuteri, Damiana; Sakurada, Tsukasa; Sakurada, Shinobu; Mizoguchi, Hirokazu; Avato, Pinarosa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Morrone, Luigi Antonio

    2017-04-11

    Preclinical studies have recently highlighted that bergamot essential oil (BEO) is endowed with remarkable neurobiolological effects. BEO can affect synaptic transmission, modulate electroencephalographic activity and it showed neuroprotective and analgesic properties. The phytocomplex, along with other essential oils, is also widely used in aromatherapy to minimize symptoms of stress-induced anxiety and mild mood disorders. However, only limited preclinical evidences are actually available. This study examined the anxiolytic/sedative-like effects of BEO using an open field task (OFT), an elevated plus-maze task (EPM), and a forced swimming task (FST) in rats. This study further compared behavioural effects of BEO to those of the benzodiazepine diazepam. Analysis of data suggests that BEO induces anxiolytic-like/relaxant effects in animal behavioural tasks not superimposable to those of the DZP. The present observations provide further insight to the pharmacological profile of BEO and support its rational use in aromatherapy.

  8. Effects of Neuroactive Drugs in the Discharge Patterns of Microsternarchus (Hypopomidae: Gymnotiformes) Electric Organ.

    Science.gov (United States)

    de Jesus, Isac Silva; Ferreira, Milena; Silva-Júnior, Urbano Lopes; Alves-Gomes, José Antônio

    2017-12-01

    Considering the conserved nature of synaptic physiology among vertebrates, we tested the effects of three psychotropics (diazepam, doxapram, and nicotine) on Microsternarchus cf. bilineatus, measuring 10 parameters associated to the electric organ discharges rhythm and waveform before and after the administration of each drug and a control group. There were statistically significant differences (p electric organ's (EO) firing rate, regardless of the expected stimulant or depressor effect of the drugs on the central nervous system (CNS). The intensity of the response changed with the treatment. The observed changes in the fishes' behavior may be a result of the drugs' direct action on the CNS or a combination of this with systemic effects of each substance tested, also in the EO.

  9. Use of Propofol for Induction and Maintenance of Anesthesia in a King Penguin ( Aptenodytes patagonicus ) Undergoing Magnetic Resonance Imaging.

    Science.gov (United States)

    Bigby, Sarah E; Carter, Jennifer E; Bauquier, Sébastien; Beths, Thierry

    2016-09-01

    Anesthesia protocols for patients with intracranial lesions need to provide hemodynamic stability, preserve cerebrovascular autoregulation, avoid increases in intracranial pressure, and facilitate a rapid recovery. Propofol total intravenous anesthesia (TIVA) maintains cerebral blood flow autoregulation and is considered superior to inhalant agents as an anesthetic protocol for patients with intracranial lesions. A propofol-based TIVA subsequent to premedication with medetomidine and diazepam was used in a king penguin ( Aptenodytes patagonicus ) undergoing magnetic resonance imaging of the brain after a new onset of seizures. This protocol provided a rapid and smooth induction and calm recovery in the penguin. When ventilation control is possible, propofol TIVA may be a superior choice to inhalant agents for anesthesia of birds with potential intracranial lesions.

  10. Use of sodium nitroprusside in neurosurgical cases during anesthesia with enflurane.

    Science.gov (United States)

    Vandesteene, A; Mouawad, E; Noterman, J; Deloof, T; Ewalenko, P; Genette, F

    1980-01-01

    In patients operated for cerebral aneurysm or angioma, the same basic method of anesthesia has been used. Premedication consisted of Thalamonal or diazepam. After induction with thiopentone, curarisation with pancuronium and tracheal intubation, anesthesia was maintained with N2O 70%, O2 30% and enflurane 1%. Small doses of fentanyl or Thalamonal were given at the beginning of anesthesia, but no more within 30 minutes before starting controlled hypotension. Adjuvant drugs and methods to reduce intracranial pressure were also used, such as dexamethasone, mannitol and cerebro-spinal fluid subtraction. The approach and dissection of the vascular lesion was done under controlled hypotension with sodium nitroprusside 0.01% solution. The mean dose of sodium nitroprusside to maintain a mean blood pressure at about 50 Torr was 1.37 mcg/kg/min.

  11. Application of radioreceptor assay of benzodiazepines for toxicology

    International Nuclear Information System (INIS)

    Aaltonen, L.; Scheinin, M.

    1982-01-01

    A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum samples from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra-assay variation < 8%, inter-assay variation < 10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas-liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affinities. (author)

  12. Voltammetric analysis of N-containing drugs using the hanging galinstan drop electrode (HGDE).

    Science.gov (United States)

    Channaa, H; Surmann, P

    2009-03-01

    The electrochemical behaviour of several N-containing voltammetric active drugs such as 1,4-benzodiazepines (chlordiazepoxide, nitrazepam and diazepam) as well as one nitro-compound (nitrofurantoin) and one azo-compound (phenazopyridine) is described using a new kind of liquid electrode, the hanging galinstan drop electrode. Concentrations of 10(-5) - 10(-8) mol L(-1) are generally measurable. Differential pulse and adsorptive stripping voltammograms are recorded in different supporting electrolytes, like 0.1 M KNO3, acetate buffer solution pH = 4.6 and phosphate buffer solution pH = 7.0. The effects of varying the starting potentials, U(start) for DPV and accumulation times, t(acc) for AdSV are considered. Briefly, it is shown that the novel galinstan electrode is suitable for reducing several functional groups in organic substances, here presented for N-oxide-, azomethine-, nitro- and azo-groups.

  13. Lafora's-like disease in a fennec fox (Vulpes zerda).

    Science.gov (United States)

    Honnold, Shelley P; Schulman, F Yvonne; Bauman, Karen; Nelson, Kevin

    2010-09-01

    A 6-yr-old captive-born female fennec fox (Vulpes zerda) had a history of multiple seizures and was treated with diazepam and phenobarbital therapy. Despite medical treatment, the seizures continued. They were intermittent and progressive, resulting in neurologic deficits and death of the animal within 6 mo of onset of the clinical signs. At necropsy, the animal was in good nutritional condition, and no gross lesions were noted in the brain. Histologically, amphophilic to basophilic, periodic acid-Schiff (PAS) positive, diastase-resistant inclusions were present in the brain, heart, and liver. Ultrastructurally, the inclusions were variably electron dense, fibrillary to occasionally granular, and non-membrane bound. The clinical, histologic, and ultrastructural findings were consistent with Lafora's disease, which in humans is a rare, fatal, autosomal recessive hereditary neurometabolic disorder characterized by progressive myoclonic epilepsy. This is the first report of Lafora's-like disease in a fennec fox.

  14. Increased thermolability of benzodiazepine receptors in cerebral cortex of a baboon with spontaneous seizures: a case report.

    Science.gov (United States)

    Squires, R; Naquet, R; Riche, D; Braestrup, C

    1979-06-01

    The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.

  15. Antiamnesic evaluation of C. phlomidis Linn. bark extract in mice Avaliação da atividade antiamnésica da casca de C. phlomidis Linn. em camundongos

    Directory of Open Access Journals (Sweden)

    anumanthachar Joshi

    2008-12-01

    Full Text Available Clerodendron phlomidis Linn. (Verbenaceae is known as Agnimantha in sanskrit. Bark of the plant is used in treating various nervous disorders. In the present study C. phlomidis was investigated for its potential as a nootropic agent in mice. The aqueous extract of the C. phlomidis (100 and 200 mg/kg, p.o. was administered for 6 successive days to both young and aged mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate short term and long term memory respectively. Scopolamine (0.4 mg/kg, i.p., diazepam (1 mg/kg, i.p. were employed to induce amnesia in mice. To delineate the mechanism by which C. phlomidis exerts nootropic action, its effect on brain acetyl cholinesterase levels were determined. Piracetam (200 mg/kg, i.p. was used as a standard nootropic agent. Pretreatment with C. phlomidis (100 and 200 mg/kg, p.o. for 6 successive days significantly improved learning and memory in mice. It reversed the amnesia induced by scopolamine, diazepam and natural ageing. It also decreased the acetyl cholinesterase levels in the whole brain. The bark of C. phlomidis can be of enormous use in the management of treatment of cognitive disorders such as amnesia and Alzheimer's disease.Clerodendron phlomidis Linn. (Verbenaceae é conhecida como Agnimantha em sânscrito. A casca da planta é utilizada no tratamento de várias disfunções neurológicas. No presente estudo, C. phlomidis foi investigada pelo seu potencial como agente nootrópico em camundongos. O extrato aquoso de C. phlomidis (100 e 200 mg/kg, p.o. foi administrado por seis dias consecutivos tanto para camundongos jovens quanto para idosos. Modelos comportamentais exteroceptivos, tais como labirinto em cruz elevada e paradigma de esquiva passiva foram empregados para avaliar memória recente e tardia, respectivamente. Escopolamina (0,4 mg/kg i.p., diazepam (1 mg/kg i.p. foram empregados para induzir amnésia em camundongos. A

  16. Ontogenic studies of the neural control of adenohypophyseal hormones in the rat: gonadotropins.

    Science.gov (United States)

    Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1990-12-01

    1. Serotonergic, dopaminergic, and opioid systems controlling luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion develop with particular characteristics in the male and female prepubertal rats. 2. Serotonergic pathways evoke a maximal release of LH and FSH in female rats from day 12 to day 20 of age, but not in males of the same age. 3. Antidopaminergic drugs increase LH and FSH levels only in the female infantile rats. This effect is absent at birth and disappears after 20 days of age. 4. Naloxone markedly increases gonadotropins in 12-day-old females. 5. On the other hand, in 12-day-old male rats some neurotropic drugs such as diazepam could enhance LH levels, the effect being absent at other ages or in female littermates. 6. A period of high sensitivity of gonadotropins to neurotropic drugs is present during the second and third weeks of life of the rat and it is related to the sexual differentiation of the brain.

  17. Effects of zoxazolamine and related centrally acting muscle relaxants on nigrostriatal dopaminergic neurons.

    Science.gov (United States)

    Matthews, R T; McMillen, B A; Speciale, S G; Jarrah, H; Shore, P A; Sanghera, M K; Shepard, P D; German, D C

    1984-05-01

    The effects of zoxazolamine (ZOX) and related centrally acting muscle relaxants on striatal dopamine (DA) metabolism and turnover, and substantia nigra zona compacta DA neuronal impulse flow were studied in rats. ZOX, chlorzoxazone and mephenesin, but not meprobamate, chloral hydrate, diazepam, pentobarbital, ethanol or dantrolene, decreased striatal DA metabolism without affecting striatal DA concentrations. More specifically, ZOX, as a representative muscle relaxant, was shown to decrease striatal DA turnover without directly affecting DA synthesis, catabolism, reuptake, or release. ZOX decreased nigral DA neuronal firing rates and dramatically decreased firing rate variability (normally many of the cells fire with bursting firing patterns but after ZOX the cells often fired with a very regular pacemaker-like firing pattern). ZOX and related centrally acting muscle relaxants appear to decrease striatal DA turnover by decreasing both neuronal firing rate and firing rate variability. The possible relationships between DA neuronal activity and muscle tone are discussed.

  18. Analysis of Drugs Interaction among Pediatric Inpatients at Hospital in Palu

    Directory of Open Access Journals (Sweden)

    Akhmed G. Sjahadat

    2013-12-01

    Full Text Available We performed drug interaction analyses in the pediatric inpatient unit at one of hospitals in Palu. In this study, those analysesstudy are important to prevent childhood morbidity, mortality and to improve patient’s safety. By using a cross-sectional descriptive study, we collected retrospective data from January until December 2012. We included patients at age of 0- 18 years old who were hospitalized during 2012 and received two or more drugs from a prescription sheet. In particular, we excluded pediatric inpatients in emergency and intensive care units who received topical medications (e.g., ointment, creams, eye drops, ear drops, and nasal drops. Each drug was analyzed by using Drug.Com software. In total, we minor interactions (44.78%. We found several drug interactions in the combination of rifampicin-isoniazid, dexamethasone-ibuprofen, acetaminophen-isoniazid, gentamicin-cefotaxime-ceftriaxone and diazepam- dexamethasone.

  19. Anaesthetic Management of a 1-Month-Old Puppy Undergoing Lateral Thoracotomy for Vascular Ring Anomaly Correction

    Directory of Open Access Journals (Sweden)

    Olga Martin Jurado

    2011-01-01

    Full Text Available A 1-month-old male flat-coated retriever was anaesthetized for correction of oesophageal constriction caused by a vascular ring anomaly. Anaesthesia was uneventfully induced with intravenous fentanyl, diazepam, and propofol and maintained with isoflurane in oxygen and air. An intercostal block with bupivacaine and lidocaine was performed, and additional analgesia with an infusion of fentanyl was provided. Fluid therapy consisted in 5% glucose in lactated Ringer’s solution and hetastarch 6%, which proved adequate to maintain normoglycemia and normovolemia. A lateral thoracotomy was performed, and the ligamentum arteriosum was ligated. Intraoperatively, heart rate (HR varied between 120 and 180 beats min−1 without accompanying changes in blood pressure. No arrhythmias were observed or bleeding occurred. The dog recovered uneventfully. Postoperative analgesia consisted in fentanyl infusion adjusted to the patient's requirement and metamizol. This paper describes for the first time the use of balanced anaesthesia and multimodal analgesia in a paediatric dog undergoing thoracotomy.

  20. Disruption of the Acyl-CoA binding protein gene delays hepatic adaptation to metabolic changes at weaning

    DEFF Research Database (Denmark)

    Neess, Ditte; Marcher, Ann-Britt; Bloksgaard, Maria

    The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an evolutionary conserved intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity. ACBP is thought to act as an acyl-CoA transporter, and in vitro analyses have indicated that ACBP can transport acyl......-CoA esters between different enzymatic systems. However, little is known about the in vivo function in mammalian cells. We have generated mice with targeted disruption of ACBP (ACBP-/-). These mice are viable and fertile and develop normally. However, around weaning the ACBP-/- mice show decreased growth......) family, around the weaning period. As a result, the hepatic de novo cholesterogenesis is significantly decreased at weaning. The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP...

  1. Quantitative analysis of abused drugs in physiological fluids by gas chromatography/chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Foltz, R.L.

    1978-01-01

    Methods have been developed for quantitative analysis of commonly abused drugs in physiological fluids using gas chromatography/chemical ionization mass spectrometry. The methods are being evaluated in volunteer analytical and toxicological laboratories, and analytical manuals describing the methods are being prepared. The specific drug and metabolites included in this program are: Δ 9 -tetrahydrocannabinol, methadone, phencyclidine, methaqualone, morphine, amphetamine, methamphetamine, mescaline, 2,5-dimethoxy-4-methyl amphetamine, cocaine, benzoylecgonine, diazepam, and N-desmethyldiazepam. The current analytical methods utilize relatively conventional instrumentation and procedures, and are capable of measuring drug concentrations as low as 1 ng/ml. Various newer techniques such as sample clean-up by high performance liquid chromatography, separation by glass capillary chromatography, and ionization by negative ion chemical ionization are being investigated with respect to their potential for achieving higher sensitivity and specificity, as well as their ability to facilitate simultaneous analysis of more than one drug and metabolite. (Auth.)

  2. Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes.

    Science.gov (United States)

    Miller, J. A.; Richter, J. A.

    1985-01-01

    The effects of several anticonvulsant drugs on sodium-dependent high affinity choline uptake (HACU) in mouse hippocampal synaptosomes was investigated. HACU was measured in vitro after in vivo administration of the drug to mice. HACU was inhibited by drugs which have in common the ability to facilitate gamma-aminobutyric acid (GABA) transmission, pentobarbitone, phenobarbitone, barbitone, diazepam, chloridiazepoxide, and valproic acid. Dose-response relationships were determined for these drugs and the drugs' potencies at inhibiting HACU correlated well with their anticonvulsant potencies. Clonazepam, ethosuximide, carbamazepine, and barbituric acid had no effect on HACU in the doses used while phenytoin and trimethadione stimulated HACU. These results suggest that certain anticonvulsants may elicit a part of their anticonvulsant activity by modulating cholinergic neurones. This effect may be mediated through a GABA mechanism. PMID:3978310

  3. Fatty acid and drug binding to a low-affinity component of human serum albumin, purified by affinity chromatography

    DEFF Research Database (Denmark)

    Vorum, H; Pedersen, A O; Honoré, B

    1992-01-01

    Binding equilibria for decanoate to a defatted, commercially available human serum albumin preparation were investigated by dialysis exchange rate determinations. The binding isotherm could not be fitted by the general binding equation. It was necessary to assume that the preparation was a mixture...... of two albumin components about 40% of the albumin having high affinity and about 60% having low affinity. By affinity chromatography we succeeded in purifying the low-affinity component from the mixture. The high-affinity component, however, could not be isolated. We further analyzed the fatty acid...... and drug binding abilities of the low-affinity component. The fatty acids decanoate, laurate, myristate and palmitate were bound with higher affinity to the mixture than to the low-affinity component. Diazepam was bound with nearly the same affinity to the low-affinity component as to the albumin mixture...

  4. Safe physiotherapy interventions in large cervical disc herniations.

    LENUS (Irish Health Repository)

    Keramat, Keramat Ullah

    2012-01-01

    A 34-year-old woman was seen in a physiotherapy department with signs and symptoms of cervical radiculopathy. Loss of cervical lordosis and a large paracentral to intraforaminal disc prolapse (8 mm) at C5-C6 level was reported on MRI. She was taking diclofenac sodium, tramadol HCl, diazepam and pregabalin for the preceding 2 months and no significant improvement, except temporary relief, was reported. She was referred to physiotherapy while awaiting a surgical opinion from a neurosurgeon. In physiotherapy she was treated with mobilisation of the upper thoracic spine from C7 to T6 level. A cervical extension exercise was performed with prior voluntary extension of the thoracic spine and elevated shoulders. She was advised to continue the same at home. General posture advice was given. Signs and symptoms resolved within the following four sessions of treatment over 3 weeks. Surgical intervention was subsequently deemed unnecessary.

  5. The liberal state and the rogue agency: FDA’s regulation of drugs for mood disorders, 1950s–1970s☆

    Science.gov (United States)

    Shorter, Edward

    2013-01-01

    The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into “rogues,” regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional “cop” agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions. PMID:18343498

  6. The liberal state and the rogue agency: FDA's regulation of drugs for mood disorders, 1950s-1970s.

    Science.gov (United States)

    Shorter, Edward

    2008-01-01

    The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into "rogues," regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional "cop" agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions.

  7. Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

    International Nuclear Information System (INIS)

    Hennies, H.H.; Hess, V.; Flohe, L.

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

  8. Management of rheumatic chorea: an observational study

    Directory of Open Access Journals (Sweden)

    Araújo Alexandra Prufer de Queiroz Campos

    2002-01-01

    Full Text Available BACKGROUND: Rheumatic chorea (RC has recently been linked to an antibody-mediated immune mechanism. OBJECTIVE/METHOD: To verify if this knowledge reflected in management changes we conceived a descriptive study. RESULTS: The medical charts of 20 children (13 females aged 6 to 12 years (mean 8 years, diagnosed as RC from June 1996 to June 1999, were reviewed. All patients received some medical treatment. Haloperidol was the most prescribed medication (15 patients - 75 %. Sulpiride, diazepam and valproate were also used as symptomatic treatment. Imune-modulating therapy with prednisone was prescribed for seven children. The shortest course of chorea (16 days occurred in a patient treated with prednisone. CONCLUSION: Prednisone has been prescribed for rheumatic chorea besides the traditional symptomatic approach. A great variety of antichoreic drugs are being employed.

  9. Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Hennies, H H; Hess, V; Flohe, L

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

  10. Self-reported drug use among secondary school students in two rapidly developing Nigerian towns.

    Science.gov (United States)

    Nevadomsky, J

    1982-01-01

    A 32-item standardized multiple-choice and open-ended questionnaire was completed by nearly 500 male and female secondary school students in two rapidly developing Nigerian towns. About two thirds of the students reported some exposure to alcohol, and about one quarter reported some experience with tobacco. There was much less use of caffeine, methaqualone in combination with diphenhydramine, 2-ethylamino-3-phenylorcamphane in combination with vitamins, chlordiazepoxide, diazepam, cannabis and dexamphetamine. Many students fell into the "past use" category. Parents were extremely disapproving of the use of almost any drug. Many students supported stronger penalties for the use of cannabis. Non-users claimed that drugs were dangerous to health. In addition, religious beliefs were associated with abstinence from drugs.

  11. Methodology for benzodiazepine receptor binding assays at physiological temperature. Rapid change in equilibrium with falling temperature

    International Nuclear Information System (INIS)

    Dawson, R.M.

    1986-01-01

    Benzodiazepine receptors of rat cerebellum were assayed with [ 3 H]-labeled flunitrazepam at 37 0 C, and assays were terminated by filtration in a cold room according to one of three protocols: keeping each sample at 37 degrees C until ready for filtration, taking the batch of samples (30) into the cold room and filtering sequentially in the order 1-30, and taking the batch of 30 samples into the cold room and filtering sequentially in the order 30-1. the results for each protocol were substantially different from each other, indicating that rapid disruption of equilibrium occurred as the samples cooled in the cold room while waiting to be filtered. Positive or negative cooperativity of binding was apparent, and misleading effects of gamma-aminobutyric acid on the affinity of diazepam were observed, unless each sample was kept at 37 0 C until just prior to filtration

  12. Allometric scaling of chemical restraint associated with inhalant anesthesia in giant anteaters.

    Science.gov (United States)

    Carregaro, Adriano Bonfim; Gerardi, Patrícia Molina; Honsho, Daniel Kan

    2009-04-01

    This study describes the use of allometric scaling in five giant anteaters (Myrmecophaga tridactyla) submitted for osteosynthesis, gastrostomy, or treatment of burns. Chemical restraint was performed by allometric scaling using the dog as a reference; acepromazine (0.06 mg/kg), diazepam (0.3 mg/kg), ketamine (8.8 mg/kg), and buprenorphine (5.9 microg/kg) were combined, and the animals were maintained under isoflurane anesthesia. Heart rate, respiratory rate, hemoglobin oxygen saturation, temperature, and anesthetic depth were measured. Postoperative treatment consisted of ketoprofen, buprenorphine, and ceftiofur. Anesthetic induction was obtained in 10-15 min, achieving muscle relaxation and absence of excitement. Physiologic parameters were stable during the procedures, and postoperative treatment was effective. Allometric scaling was effective for chemical restraint and postoperative treatment.

  13. Anti-convulsant therapy in eclampsia.

    Directory of Open Access Journals (Sweden)

    Maheshwari J

    1989-04-01

    Full Text Available Seventy four patients presented with eclampsia at N.W.M. Hospital. Bombay. Among the patients with eclampsia, 64.9% were primis, 29.7% were gravida II-IV and 5.4% were grand multis. As many as 40.5% patients were less than 20 years of age, while 2.7% were over 30 years of age. 48.7% had antepartum convulsions, 40.5% had intrapartum convulsions, while 8 patients convulsed in the postpartum period. Besides standard management of eclamptic patients, 3 protocols of anticonvulsant therapy were utilised. 27% were managed with diphenyl hydantoin sodium, 43% with magnesium sulphate, and 30% by combination of diazepam and pentazocine. The maternal and perinatal outcome was evaluated. Control of convulsions was superior with magnesium sulphate while perinatal outcome was best with diphenyl hydantoin.

  14. [Case with difficulty in differentiating between transient neuroleptic malignant syndrome and catatonia after neuroleptic analgesia].

    Science.gov (United States)

    Yanagawa, Youichi; Miyazaki, Masaki

    2010-02-01

    An 18-year-old woman was treated with neuroleptic analgesia using fentanyl, morphine, droperidol and haloperidol for general anesthesia and pain control for her knee operation. Postoperatively, she showed emotional unstableness, following dyspnea, tachycardia, fever, hyperhydrosis, muscle rigidity and myoclonus like involuntary movement. She received infusion of 140 mg dantrolene in total under suspicion of having neuroleptic malignant syndrome, but her symptoms improved slightly. After being transferred to our hospital, she exhibited immobility, mutism, rigidity, and catalepsy, and she was suspected of having lethal catatonia. Infusion of diazepam 10 mg resulted in dramatical improvement of her symptoms. Differential diagnosis between neuroleptic malignant syndrome and catatonia is difficult; however, a first line therapy is differential diagnosis. Thus, physician should consider catatonia when treating neuroleptic malignant like syndrome.

  15. The Report of Suicide by Ingestion of Lidocaine Topical Spray

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    Hossein Hassanian-Moghaddam

    2014-09-01

    Full Text Available Background: Lidocaine is a local anesthetic and antiarrhythmic agent. There are reports on accidental and intentional cases of poisoning following injection of lidocaine while rare are the fatal cases realized after oral ingestion of lidocaine. Suicidal poisoning with lidocaine pharmaceutical formulations is rare since no pharmaceutical dosage forms for oral use are available except gels and sprays used as local anesthetics in dentistry. Cases: Three cases of suicidal poisoning by ingestion of the content of lidocaine topical spray are reported in the present study. The cases developed episodes of seizure requiring diazepam and other therapeutic modalities upon admission. Eventually, one of the cases expired. Conclusion: To the best of our knowledge, this study is the first reported case of suicidal poisoning after ingestion of this formulation which highlights the fact that lidocaine topical spray formulation may be used for committing suicide. Ingestion of lidocaine present in topical spray can induce varying levels of toxicity that can even be fatal.

  16. Perception and knowledge about narcotics among nurses

    Directory of Open Access Journals (Sweden)

    Desai Geetha

    2003-01-01

    Full Text Available Aim: To determine the extent to which nurses are able to correctly identify drugs as narcotics and to ascertain their perception of the addiction potential of opiates when used for pain management. Methods: A questionnaire was administered to 86 nurses who attended palliative care workshops in India. Findings: Only morphine (95%, heroin (71% and codeine (75% were correctly identified as narcotics by the majority of participants. Imipramine (34%, diazepam (20% and phenobarbitone (39% were wrongly classified as narcotics by many nurses. Dextropropoxyphene (11%, pentazocine (21%, buprenorphine (15% were correctly classified as narcotics by fewer than half the participants. Only 14% knew that that the frequency of psychological dependence due to use of morphine for cancer pain was less than 1%.

  17. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))

    1984-03-16

    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

  18. Utilização de benzodiazepínicos no Serviço Municipal de Saúde de Coronel Fabriciano, Minas Gerais Use of benzodiazepines in local public health services in Coronel Fabriciano in the State of Minas Gerais

    Directory of Open Access Journals (Sweden)

    Karleyla Fassarelo Firmino

    2012-01-01

    Full Text Available Neste estudo foram avaliadas as indicações de benzodiazepínicos no Serviço Municipal de Saúde de Coronel FabricianoMG, verificando sua conformidade com o preconizado pela literatura. O estudo avaliou todas as receitas desses medicamentos provenientes das Unidades Municipais de Saúde no período de Setembro a Outubro de 2006, os formulários de indicação clínica preenchidos pelo prescritor e cadastros informatizados do serviço. Analisaram-se 1.866 receitas, sendo 59,7% do Diazepam e o restante do Clonazepam. A Dose Diária Definida por mil habitantes por dia foi de 24,69 para o Diazepam e de 3,58 para o Clonazepam. Cerca de 50% das indicações relatadas pelos médicos foram como hipnótico ou ansiolítico, 21,9% para "uso crônico/dependência" e o restante para outras indicações. Das receitas que atenderam aos critérios de inclusão para análise da adequação da indicação (1618, cerca de 70% foram consideradas não adequadas, tendo em vista a indicação e o tempo de tratamento. Houve um alto percentual de inadequação na utilização de benzodiazepínicos, principalmente pelo uso prolongado e para atender a casos considerados pelos prescritores como uso crônico/dependência. Assim, há responsabilidade do serviço de saúde na manutenção da dependência.In this study, indications for benzodiazepines in the healthcare services of the city of Coronel Fabriciano (State of Minas Gerais, Brazil were analyzed in terms of compliance with the indications established in the literature. The study was carried out using all prescriptions for benzodiazepines in municipal healthcare units between September and October 2006, as well as the prescription form filled out by the prescriber and computer files. A total of 1866 prescriptions were analyzed; 59.7% were for diazepam and the rest were for clonazepam. The mean daily dose per 1000 inhabitants/day was 24.69 for diazepam and 3.58 for clonazepam. Approximately 50% of the indications

  19. Detection of illicit drugs in impaired driver saliva by a field-usable SERS analyzer

    Science.gov (United States)

    Shende, Chetan; Huang, Hermes; Farquharson, Stuart

    2014-05-01

    One of the greatest dangers of drug use is in combination with driving. According to the most recent National Highway Traffic Safety Administration (NHTSA) studies, more than 11% of drivers tested positive for illicit drugs, while 18% of drivers killed in accidents tested positive for illicit, prescription or over-the-counter drugs. Consequently, there is a need for a rapid, noninvasive, roadside drug testing device, similar to the breathalyzers used by law enforcement officials to estimate blood alcohol levels of impaired drivers. In an effort to satisfy this need we have been developing a sampling kit that allows extraction of drugs from 1 mL of saliva and detection by surfaceenhanced Raman spectroscopy using a portable Raman analyzer. Here we describe the development of the sampling kit and present measurements of diazepam at sub μg/mL concentrations measured in ~15 minutes.

  20. Oral versus intravenous premedication for small bowel biopsy in children: effect on procedure and fluoroscopy times.

    Science.gov (United States)

    Stenhammar, L; Wärngård, O; Lewander, P; Nordvall, M

    1993-01-01

    Oral alimemazine and cisapride, or diazepam and cisapride, or iv midazolam and metoclopramide were given as premedication for small bowel biopsy to three groups of children from a total population of 185 individuals. The biopsy procedures were performed under intermittent fluoroscopy and times for both were recorded. The median biopsy procedure time was significantly shorter in children given iv midazolam and metoclopramide (6 min) compared to those given oral premedication (10 min) (p < 0.001). The median fluoroscopy time was very short in all groups, ranging between 3 and 6 s. It is concluded that iv premedication is superior to oral premedication for small bowel biopsy in children because more effective sedation is obtained.

  1. Pharmacological evaluation of bee venom and melittin

    Directory of Open Access Journals (Sweden)

    Camila G. Dantas

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  2. Caudal anesthesia in pediatric surgical practice.

    Science.gov (United States)

    Rahman, S; Siddiqui, M A; Haque, M; Majumder, S K; Ali, M S; Majid, M A; Hasan, M R

    2006-07-01

    Prospective study was carried out on 100 patients since May 2005 in my private practice and in the department of pediatric surgery of MMCH. Under caudal anesthesia along with or without ketaminie induction and gas inhalation all the patients underwent different surgical procedure namely anorectal surgery (eg. anoplasty, rectal polyp), urogenital surgery (Circumcision, hypospadias, meatotomy), groin surgery (hernia, hydrocele) and foot & leg surgery. Calculated dose schedule of drugs used in anesthesia and volume were maintained. Time of giving anesthesia and time of starting analgesia were recorded. Per-operative and postoperative analgesia were evaluated. Every parent was explained regarding the merit of caudal anesthesia calculated and compared with that of general anesthesia. Application of caudal anesthesia with or without ketamine & diazepam induction can be used safely and cost effectively and may be put into protocol in many of the pediatric surgical practice both in institute and also in private practice.

  3. Neonatal tetanus associated with skin infection.

    Science.gov (United States)

    Maharaj, M; Dungwa, N

    2016-08-03

    A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period.

  4. Diagnosis and management of tetanus outside the intensive care unit: a case report

    Science.gov (United States)

    Bravo, T. E.; Siregar, M. L.; Jamil, K. F.

    2018-03-01

    Tetanus is an acute, toxin-mediated disease caused by Clostridium tetani infection. Under favorable anaerobic conditions, such as in the unclean environment, necrotic wounds, this ubiquitous bacillus may produce tetanospasmin, an extremely potent neurotoxin. A 38-year-old man was admitted to an emergency room, at Zainoel Abidin General Hospital, with the main complaint of back-muscle stiffness. Based on physical examination, he was fully alert with a slightly rapid breathing, trismus with the maximum oral cavity opening was only about one finger width, but rhisus sardonicus was not evident. Ten days before admission, while gardening, his left foot accidentally stabbed by wooden tree stake. We immediately started a single dose of tetanus immunoglobulin followed by intravenous metronidazole, penicillin G, and intravenous diazepam. Tetanus diagnosed by physical clinical finding. The management of tetanus patients including the use of immunoglobulin and antibiotic therapy, analgesia, sedation and neuromuscular blockade management and mechanical ventilation, the care was delivered outside the Intensive care unit.

  5. Early Activation of Children Operated on under Extracorporeal Circulation

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    P. R. Dudov

    2008-01-01

    Full Text Available Objective: to study the safety and clinical and economic efficiency of early activation of children operated on under extracorporeal circulation (EC. Subjects and methods. Sixty-eight children aged 4—14 years (8.6±0.4 years operated on under EC for congenital heart diseases (CHD were examined. In accordance with the time of switching to spontaneous respiration and tracheal extubation, 2 groups were identified: 1 those who received postoperative artificial ventilation (AV for 2.9±0.2 hours (a study group; 2 those who had AV for 8.7±0.7 hours (a control group. Both groups did not differ in age, cardiac diseases, their severity, anthropometric characteristics, EC duration, aortic ligation time, and abnormality pattern. In the study group, anesthesia was maintained with fentanyl (5.3±0.1 ^g/kg/hr, diazepam (0.15±0.01 mg/kg/hr, and inhaled ftorotan or enflurane. Diazepam was discontinued in the postperfusion period. The control group received fentanyl (7.6±0.4 ^Bg/kg/hr, diazepam (0.3±0.02 mg/kg/hr, droperidol (0.4±0.04 mg/kg/hr, and/or sodium oxybutyrate (81±5 mg/kg/hr. Myoplegia was provided by pancuronium or pipecuronium that was continuously infused until EC was completed in Group 1 and intermittently injected until the end of surgery in Group 2. Results. There were no indications for tracheal reintubation in both groups of patients. The early postoperative period was uncomplicated in 97.2% of the children in the study group and in 28.1% in the control group (p<0.05. The incidence of pulmonary complications was 2.8 and 46.9%, respectively (p<0.05. In the children from Groups 1 and 2, the duration of a resuscita-tive period was 44.2±1.7 and 77.3±4.9 hours, respectively (p<0.05, and that of the whole postoperative period was 12.6±0.3 and 18.0±1.1 days (p<0.05. In the study group, the total final expenditures, including the cost of anesthesia and treatment for postoperative complications, decreased by 127.5% as compared to the control

  6. [Idiopathic rabbit syndrome: a case report].

    Science.gov (United States)

    Miwa, H; Sasaki, Y; Hatori, K; Tanaka, S; Mizuno, Y

    1999-10-01

    We report a patient with idiopathic oromandibular tremor resembling rabbit syndrome. The patient is a 36-year-old Japanese woman without any past and medical histories. On neurological examination, there was no abnormal finding except the oromandibular tremor. The tremor was confined to the jaw and perioral muscles. There was no extremity tremor. Laboratory findings were all normal, as well as her MRI and EEG. Surface EMG studies revealed that regular grouped discharges at a frequency of about 6 Hz appeared in the masseter, the orbicularis oris, and the digastric, and that the alternative contractions were found between the masseter and the digastric. Oral administration of tiapride was effective, but diazepam, trihexyphenydil, levodopa, and a beta-blocker were without effect. Although she had not taken neuroleptics, the appearance of the tremor was identical to the rabbit syndrome. The efficacy of the dopamine blockade may suggest that an abnormal basal ganglia function contributes to the pathophysiologic mechanism underlying this type of tremor.

  7. An Updated View of Translocator Protein (TSPO

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    Nunzio Denora

    2017-12-01

    Full Text Available Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO, first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery. This special issue was programmed with the aim of summarizing the latest findings about the role of TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or therapeutics. A total of 9 papers have been accepted for publication in this issue, in particular, 2 reviews and 7 primary data manuscripts, overall describing the main advances in this field.

  8. Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

    Science.gov (United States)

    Pal, Dilipkumar

    2008-01-01

    The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

  9. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

  10. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

  11. Caring for patients with rabies in developing countries - the neglected importance of palliative care.

    Science.gov (United States)

    Tarantola, Arnaud; Crabol, Yoann; Mahendra, Bangalore Jayakrishnappa; In, Sotheary; Barennes, Hubert; Bourhy, Hervé; Peng, Yiksing; Ly, Sowath; Buchy, Philippe

    2016-04-01

    Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource-limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries. © 2016 John Wiley & Sons Ltd.

  12. The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat

    International Nuclear Information System (INIS)

    Hemmingsen, R.; Braestrup, C.; Nielsen, M.; Barry, D.I.

    1982-01-01

    The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 31/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on 3 H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (Ksub(D)) and the maximal number of binding sites (Bsub(max)) for 3 H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causual part in physical ethanol dependence. (author)

  13. Synthesis of high specific activity tritium labelled compounds

    International Nuclear Information System (INIS)

    Parent, P.

    1986-01-01

    Tritiated methyl iodide of high specific activity is synthetized by Fischer-Tropsch reaction of tritium with carbon monoxide, tritiated methanol obtained is reacted with hydriodic acid. It is used for the synthesis of S-adenosyl L-methionine 3 H-methyl and of diazepam 3 H-methyl derivatives. Synthesis of 3-PPP 3 H: (hydroxy-3 phenyl)-3N-n propyl [ 3 H-2.3] piperidine [ 3 H-2.3] with a specific activity of 4.25 T Bq/mM (115 Ci/mM) and of baclofene 3 H with a specific activity of 0.925 TBq (25 Ci/mM) are also described [fr

  14. Female spouses of injection drug users in Pakistan: a bridge population of the HIV epidemic?

    Science.gov (United States)

    Ahmad, S; Mehmood, J; Awan, A B; Zafar, S T; Khoshnood, K; Khan, A A

    2011-04-01

    An estimated 21% of injection drug users (IDUs) in Pakistan are HIV-positive and data suggest that the spouses of IDUs may be a critical component of the HIV transmission chain. This study interviewed 101 spouses of male IDUs about their sexual practices and drug use. We found that 43% had been sexually active with their partners in the past month but only 4% reported selling sex. Almost a quarter (23%) used drugs and 19% injected drugs, usually a combination of diazepam and pheniramine. Although sex work was infrequent among spouses of IDUs, their risk of contracting HIV and transmitting it to others was high because they received injection drugs, sometimes along with their IDU husbands, from the same health centres that provided therapeutic injections to the rest of the community. IDU spouses may thus serve as a bridge group via therapeutic injections, rather than via sex work.

  15. Efeito de medicamentos sobre tipos eletroclínicos de crises epilépticas na síndrome de Lennox-Gastaut

    Directory of Open Access Journals (Sweden)

    José Geraldo Speciali

    1977-09-01

    Full Text Available Analisamos os resultados terapêuticos obtidos com o uso de diferentes drogas (diazepam, nitrazepam, clonazepam, difenilhidantoina, barbitúricos - fenobarbital e primidona -, dipropilacetato de sódio e ACTH em 29 pacientes com síndrome de Lennox-Gastaut. Discutimos a ação de cada droga sobre as crises epilépticas (tônicas, tônico-clônicas, clônicas, mioclônicas ou mioclonoatônicas, atônicas e ausências atípicas durante o primeiro mês de cada esquema terapêutico. Delimitamos os campos de ação específica de cada medicação e verificamos a possibilidade de reduzir a incidência de crises epilépticas retirando ou diminuindo as dosagens das drogas administradas.

  16. Propylene Glycol Poisoning From Excess Whiskey Ingestion

    Directory of Open Access Journals (Sweden)

    Courtney A. Cunningham MD

    2015-09-01

    Full Text Available In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

  17. Delirium in the course of dependence upon gamma-butyrolactone (GBL - a case report

    Directory of Open Access Journals (Sweden)

    Łobejko Łukasz

    2016-12-01

    Full Text Available Gamma-butyrolactone (GBL is an organic chemical compound of the lactones group, undergoing biotransformation into gamma-hydroxybutyrate after the intake (GHB. Because of the easy access, low price and fast psychotropic effect, GBL is becoming increasingly popular substance having intoxicating effect. Taking of GBL causes dose-dependent euphoric, sedative, hypnotic effects. Its use can quickly lead to physical dependence with severe course of withdrawal syndromes. Withdrawal symptoms resemble those occurring in the course of addiction to alcohol or benzodiazepines. In some patients, delirium develops during substance withdrawal. There are described severe, life-threatening complications in the course of delirium in GBL-dependent patients. The management of withdrawal syndromes and delirium mainly involves administration of benzodiazepines. In this paper, we present a case of delirium in 24-year-old man addicted to GBL hospitalized in a psychiatric ward. Delirium in this patient went without complications and was successfully managed with diazepam and lorazepam.

  18. The effect of GABAmimetics on the duration of immobility in the forced swim test in albino mice.

    Science.gov (United States)

    El Zahaf, Najwa Ahmed; Salem Elhwuegi, Abdalla

    2014-01-01

    Studies regarding the role of gamma aminobutyric acid (GABA) in depression are conflicting. Therefore, it was decided to examine the effect of different drugs that enhance the GABA system on the time of immobility induced by the forced swim test (FST). Adult albino mice were divided into several groups of six animals. Each group received an intraperitoneal injection of either imipramine (10, 20, or 30 mg/kg), diazepam (0.5, 1, or 2 mg/kg), vigabatrin (100, 200, or 300 mg/kg), zolpidem (2.5, 5, or 10 mg/kg), or alprazolam (1, 2.5, or 5 mg/kg). Control groups received the appropriate vehicle. One hour after injection, the duration of immobility was measured for 5 min in the FST. The percentage change in the duration of immobility from the control was calculated for each group. The statistical test of the difference between the treated and the control groups was calculated using unpaired Student's t-test. Imipramine produced a significant dose-dependent decrease in the duration of immobility (78, 74, and 56%, respectively). Different doses of diazepam, vigabatrin, and zolpidem produced a significant increase in the duration of immobility (119, 126, and 128%), (116, 124, and 128%), and (108, 109, and 119%), respectively. The two low doses of alprazolam produced a significant increase (115 and 120%), while the high dose produced a significant decrease in the duration of immobility (74%). Increasing central GABAergic activity by different mechanisms has resulted in a depressant-like activity measured as an increase in the duration of immobility in the FST model of depression.

  19. Status epilepticus: Role for etiology in determining response to benzodiazepines.

    Science.gov (United States)

    Joshi, Suchitra; Rajasekaran, Karthik; Hawk, Kyle M; Chester, Stephen J; Goodkin, Howard P

    2018-04-01

    Clinical factors contributing to benzodiazepine failure in treating status epilepticus (SE) include suboptimal dosing and seizure duration. As many benzodiazepine-refractory episodes of SE arise from acute etiologies, we sought to determine whether etiology impacts SE treatment. The potency of diazepam to terminate SE induced by lithium-pilocarpine (LiPilo-SE) or kainic acid (KA-SE) in 3-week-old rats was studied by video-electroencephalography. Synaptic γ-aminobutyric acid type A receptor (GABAR)-mediated currents were recorded from dentate granule cells using voltage-clamp electrophysiology. Surface expression of γ2 subunit-containing GABARs and Kv4.2 potassium channels in hippocampal slices was determined using a biotinylation assay. Expression of phosphorylated forms of β2/3 and γ2 subunits was determined using phosphospecific antibodies and Western blotting. Diazepam failed to terminate late SE in LiPilo-SE animals but was successful in terminating KA-SE of 1- and 3-hour duration. One hour after SE onset, GABAR-mediated synaptic inhibition and γ2 subunit-containing GABAR surface expression were reduced in LiPilo-SE animals. These were unchanged in KA-SE animals at 1 and 3 hours. Phosphorylation of γ2 subunit residue S327 was unchanged in both models, although GABAR β3 subunit S408/409 residues were dephosphorylated in the LiPilo-SE animals. Kv4.2 potassium channel surface expression was increased in LiPilo-SE animals but reduced in KA-SE animals. SE-model-dependent differences support a novel hypothesis that the development of benzodiazepine pharmacoresistance may be etiologically predetermined. Further studies are required to investigate the mechanisms that underlie such etiological differences during SE and whether etiology-dependent protocols for the treatment of SE need to be developed. Ann Neurol 2018;83:830-841. © 2018 American Neurological Association.

  20. In vitro and in vivo pharmacological characterization of a neuropeptide S tetrabranched derivative.

    Science.gov (United States)

    Ruzza, Chiara; Rizzi, Anna; Malfacini, Davide; Pulga, Alice; Pacifico, Salvatore; Salvadori, Severo; Trapella, Claudio; Reinscheid, Rainer K; Calo, Girolamo; Guerrini, Remo

    2015-02-01

    The peptide welding technology (PWT) is a novel chemical strategy that allows the synthesis of multibranched peptides with high yield, purity, and reproducibility. With this approach, a tetrabranched derivative of neuropeptide S (NPS) has been synthesized and pharmacologically characterized. The in vitro activity of PWT1-NPS has been studied in a calcium mobilization assay. In vivo, PWT1-NPS has been investigated in the locomotor activity (LA) and recovery of the righting reflex (RR) tests. In calcium mobilization studies, PWT1-NPS behaved as full agonist at the mouse NPS receptor (NPSR) being threefold more potent than NPS. The selective NPSR antagonists [ (t) Bu-D-Gly(5)]NPS and SHA 68 displayed similar potency values against NPS and PWT1-NPS. In vivo, both NPS (1-100 pmol, i.c.v.) and PWT1-NPS (0.1-100 pmol, i.c.v.) stimulated mouse LA, with PWT1-NPS showing higher potency than NPS. In the RR assay, NPS (100 pmol, i.c.v.) was able to reduce the percentage of mice losing the RR after diazepam administration and their sleep time 5 min after the i.c.v. injection, but it was totally inactive 2 h after the injection. On the contrary, PWT1-NPS (30 pmol, i.c.v.), injected 2 h before diazepam, displayed wake-promoting effects. This PWT1-NPS stimulant effect was no longer evident in mice lacking the NPSR receptor. The PWT1 technology can be successfully applied to the NPS sequence. PWT1-NPS displayed in vitro a pharmacological profile similar to NPS. In vivo PWT1-NPS mimicked NPS effects showing higher potency and long-lasting action.

  1. Effects of Retama raetam (Forssk. Webb & Berthel. (Fabaceae on the central nervous system in experimental animals

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    Al-Tubuly Rida A.

    2011-01-01

    Full Text Available Retama raetam (Forssk. Webb & Berthel. (Fabaceae, commonly known as ‘raetam’ or ‘broom bush’, is a desert shrub that grows abundantly in North-African countries, Palestine and Syria. Traditionally, this plant has been used as an abortifacient, a purgative and a vermifuge. In the present study, the effect of the methanol (MeOH extract of the aerial parts of R. raetam on the central nervous system (CNS has been evaluated using a mice model. In the photoelectrical cell test, the extract of R. raetam (ERR at a dose of 125 mg/kg body weight did not exhibit any effect on the spontaneous motor activity in mice. At a dose of 250 mg/kg body weight, ERR increased ambulatory movement, but had no effect on the non-ambulatory movement, while a dose of 375 mg/kg body weight decreased both ambulatory and non-ambulatory movements. The effect of ERR on the anxiety levels and behaviors of mice was investigated using the elevated plus-maze test. At doses of 125, 250 and 375 mg/kg body weight, ERR decreased anxiety levels without showing an effect on the total activity; it did not affect anxiety levels but increased the total activity; it increased anxiety levels and decreased the total activity, respectively. In the diazepam-induced sleep test, ERR increased the onset of sleep without affecting the duration of sleep at the dose of 250 mg/kg body weight. The dose of 375 mg/kg body weight decreased the onset of sleep while increasing the duration of sleep. ERR did not exhibit any effect on the diazepam-induced sleep in the presence of flumazenil or picrotoxin.

  2. Uptake and depuration of pharmaceuticals in aquatic invertebrates

    International Nuclear Information System (INIS)

    Meredith-Williams, Melanie; Carter, Laura J.; Fussell, Richard; Raffaelli, David; Ashauer, Roman; Boxall, Alistair B.A.

    2012-01-01

    The uptake and depuration of a range of pharmaceuticals in the freshwater shrimp (Gammarus pulex) and the water boatman (Notonecta glauca) was studied. For one compound, studies were also done using the freshwater snail Planobarius corneus. In G. pulex, bioconcentration factors (BCFs) ranged from 4.6 to 185,900 and increased in the order moclobemide < 5-fluoruracil < carbamazepine < diazepam < carvedilol < fluoxetine. In N. glauca BCFs ranged from 0.1 to 1.6 and increased in the order 5-fluorouracil < carbamazepine < moclobemide < diazepam < fluoxetine < carvedilol. For P. corneus, the BCF for carvedilol was 57.3. The differences in degree of uptake across the three organisms may be due to differences in mode of respiration, behaviour and the pH of the test system. BCFs of the pharmaceuticals for each organism were correlated to the pH-corrected liposome–water partition coefficient of the pharmaceuticals. - Highlights: ► One of the first studies exploring the uptake of pharmaceuticals into aquatic invertebrates. ► Data presented on uptake, depuration rates and bioconcentration for a range of pharmaceuticals. ► Uptake is correlated with the pH-corrected liposome–water partition coefficient. ► Findings can be used to better predict impacts of pharmaceuticals on the aquatic environment. - The factors affecting the degree of uptake of pharmaceuticals into aquatic invertebrates were studied. The results indicate that species traits such as respiration and behaviour of the organisms and pH-corrected liposome–water partition coefficients are important factors in determining pharmaceutical uptake.

  3. Validation and pharmacological characterisation of MK-801-induced locomotor hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics.

    Science.gov (United States)

    Bradford, Andrea M; Savage, Kevin M; Jones, Declan N C; Kalinichev, Mikhail

    2010-10-01

    We evaluated locomotor hyperactivity induced in BALB/C mice by an N-methyl-D-aspartate receptor antagonist MK-801 as an assay for the detection of antipsychotic drugs. We assessed the effects of antipsychotic drugs to validate the assay (study 1), selective dopamine and serotonin ligands for pharmacological characterisation of the model (study 2) and a number of compounds with efficacy in models of schizophrenia to understand the predictive validity of the model (study 3). Adult males (n  = 9/group) were pretreated with a test compound, habituated to locomotor activity cages before receiving MK-801 (0.32 mg/kg) and activity recorded for a further 75 or 120 min. In study 1, we tested haloperidol, clozapine, olanzapine, risperidone, ziprasidone, aripiprazole, sertindole and quetiapine. In study 2, we tested SCH23390 (D(1) antagonist), sulpiride (D(2)/D(3) antagonist), raclopride (D(2)/D(3) antagonist), SB-277011 (D(3) antagonist), L-745,870 (D(4) antagonist), WAY100635 (5-HT(1A) antagonist), 8-OH-DPAT (5-HT(1A) agonist), ketanserin (5-HT(2A)/5-HT(2C) antagonist) and SB-242084 (5-HT(2C) antagonist). In study 3, we tested xanomeline (M(1)/M(4) receptor agonist), LY379268 (mGluR2/3 receptor agonist), diazepam (GABA(A) modulator) and thioperamide (H(3) receptor antagonist). All antipsychotics suppressed MK-801-induced hyperactivity in a dose-dependent and specific manner. The effects of antipsychotics appear to be mediated via dopamine D(1), D(2) and 5-HT(2) receptors. Xanomeline, LY379268 and diazepam were active in this assay while thioperamide was not. MK-801-induced hyperactivity in BALB/C mice model of positive symptoms has shown predictive validity with novel compounds acing at M(1)/M(4), mGluR2/3 and GABA(A) receptors and can be used as a screening assay for detection of novel pharmacotherapies targeting those receptors.

  4. Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

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    Lauren Z. Gashlin

    2015-03-01

    Full Text Available Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs may cause delirium and over-sedation. Phenobarbital (PBT is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group or BZDs with adjunctive PBT (PBT-adjunct group. The patients received at least one dose of PBT in addition to BZDs (variable doses in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6% in the PBT-adjunct group and 5 patients (23.8% in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588. The median (IQR duration of withdrawal symptoms was 44 (12-62 hours in the PBT-adjunct group compared to 53 (37-87 hours in the BZD only group, with no significant difference between the groups (P = 0.249. The median (IQR cumulative BZD dose requirement (diazepam equivalent in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226 vs. 326 (160-550 mg, P = 0.02. Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing.

  5. Accelerated neuroregulation for therapy of opiate dependency

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    S. Sunatrio

    2004-03-01

    Full Text Available Acute weaning from chronic opioid abuse during general anesthesia is usually followed by adrenergic outflow effects. This article is to report our experience with accelerated neuroregulation that reverses the physical and psychological dependency. After a comprehensive psychological and medical examination, 361 heroin dependent patients were admitted to ICU to be hospitalized for a full 24 or 36 hours, including a 6 hour pre-procedure medication process (solbutamol, clonidine, diazepam, ranitidine, omeprazole, vitamin C, octreotide, and ondansetron. Anesthesia was induced with midazolam and propofol iv and maintained with propofol infusion. Naltrexon, clonidine, octreotide, and diazepam were then administered. Anesthesia was maintained for 3 ½ - 5 hours depending on severity of withdrawal symptoms precipitated by naltrexone. Analgetics and sedatives were given as needed afterwards. Upon discharge on the following day, patient was prescribed a regimen of oral naltrexone for 10-12 months. All 361 patients were successfully detoxified without any adverse anesthetic events. The side effects encountered were fatigue, insomnia, drowsy, shivering, abdominal pain, nausea, diarrhoea, myalgia, goose bumps and uncomfortable feeling. In most of the patients these symptoms disappeared without any treatment. Symptomatic treatments were needed in 32.7% of patients. In all 166 patients who completed their naltrexone maintenance treatment, craving disappeared in the 10th month. The main problem was the low patient compliance to oral naltrexone, so that only 45.9% of the patients completed their therapy. Conclusion: Accelerated neuroregulation which includes naltrexone maintenance treatment (10-12 months was highly effective to detoxify and to abolish craving in the heroin dependent patients. (Med J Indones 2004; 13: 53-8Keywords: detoxification, craving management

  6. Management protocols for status epilepticus in the pediatric emergency room: systematic review article.

    Science.gov (United States)

    Au, Cheuk C; Branco, Ricardo G; Tasker, Robert C

    This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department treatment of status epilepticus. Systematic search of national or regional guidelines (January 2000 to February 2017) contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 emergency department guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11) guidelines recommended phenytoin, but other options were phenobarbital (nine/11), valproic acid (six/11), and either fosphenytoin or levetiracetam (each four/11); third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital). All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

    Science.gov (United States)

    Kreiss, Deborah S; Coffman, Catherine F; Fiacco, Nicholas R; Granger, Jason C; Helton, Bernadette M; Jackson, Jennifer C; Kim, Leonid V; Mistry, Rishi S; Mizer, Tammie M; Palmer, Lolita V; Vacca, Jay A; Winkler, Stuart S; Zimmer, Benjamin A

    2013-03-01

    Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD. Copyright © 2013. Published by Elsevier Inc.

  8. Pulmonary thromboembolism and sudden death in psychiatric patients: Two cases reports

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    Marinković Nadica

    2017-01-01

    Full Text Available Introduction. Pulmonary thromboembolism occurs usually by running a thrombus from the deep veins of the legs rarely periprostatic or periuteric veins. Virchow's triad of necessary conditions for the occurrence of thrombosis involves disruption of blood flow, disruption of blood chemistry and damage to the vessel wall. Venous thrombosis is often associated with the implementation of antipsychotic therapy. Case report. We reported two cases of sudden death of psychiatric patients who were in both cases fixed during hospitalization. The first case was a 26-year-old woman treated a year with the diagnose of postpartum reactive psychosis. She was hospitalized because of mental state worsening with a dominant depressed mood, visual and auditory hallucinations. Her therapy was determined by diazepam, clozapine, haloperidol and lamotrigine. Suddenly, the patient died on the fifth day of hospitalization. The autopsy showed massive thromboembolism of the pulmonary artery branches. Toxicological analysis revealed the presence of therapeutic doses of antipsychotics. The second case was a-45-yearold men, a long-time alcoholic. On admission, the diagnosis of delirium tremens was established, and diazepam and haloperidol were administered. On the fifth day of hospitalization, he suddenly died. The autopsy showed thromboembolism of the branch of the pulmonary artery. Toxicological analysis established the presence of nordiazepam in urine (0.06 mg/L. Both patients were fixed during hospitalization. Conclusion. Both presented psychiatric patients were younger than 50 years, were not overweight, did not have changes of the venous blood vessels. Nowadays, when the issue of medical responsibility often arises in these and similar cases of sudden death in patients treated in psychiatric clinics, the questions on medical malpractice could be expected.

  9. Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model

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    Brandon Kar Meng Choo

    2018-02-01

    Full Text Available Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish.

  10. Effect of combination of Phyllanthus emblica, Tinospora cordifolia, and Ocimum sanctum on spatial learning and memory in rats

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    Harshad O Malve

    2014-01-01

    Full Text Available Background: There has been a steady rise in number of patients suffering from dementia including dementia associated with Alzheimer′s disease. Effective treatment of Alzheimer′s disease dementia is an unmet medical need. Objective: To evaluate effects of formulation containing combination of Phyllanthus emblica (Pe and Tinospora cordifolia (Tc with and without Ocimum sanctum (Os on learning and memory performance of normal and memory impaired rats in complex maze and compare with effects of Tinospora cordifolia and Phyllanthus emblica alone. Materials and Methods: Wistar rats; either sex (100-150 g were divided in seven groups Control, Piracetam, Rivastigmine, Tc, Pe, Formulation 1 (Tc + Pe, and Formulation 2 (Tc + Pe + Os.The study was divided in four parts: In part 1 memory enhancement was tested in normal rats. In part 2, 3, and 4 the effects of drugs were tested in Scopolamine-, Diazepam-, and Cyclosporine-induced amnesia. Hebb-Williams maze was used to test for learning and memory. Time required to trace food and number of errors in maze were noted. Results: In normal rats, all test drugs showed significant reduction in time required to trace the food and number of errors after 24 h compared with vehicle control. Formulations 1 and 2 reduced the time required to trace food and number of errors and the results were comparable with positive control groups and comparators Tc and Pe. Formulations 1 and 2 reversed amnesia produced by Scopolamine, Diazepam, and Cyclosporine when compared with vehicle control and showed comparable results with those of positive control groups and comparators Tc and Pe. Conclusion: Formulations 1 and 2 demonstrated nootropic activity and both the formulations showed comparable nootropic activity with that of Tc and Pe alone.

  11. Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds.

    Science.gov (United States)

    Patterson, John P; Markgraf, Carrie G; Cirino, Maria; Bass, Alan S

    2005-01-01

    A series of experiments were undertaken to evaluate the accuracy, precision, specificity, and sensitivity of an automated, infrared photo beam-based open field motor activity system, the MotorMonitor v. 4.01, Hamilton-Kinder, LLC, for use in a good laboratory practices (GLP) Safety Pharmacology laboratory. This evaluation consisted of two phases: (1) system validation, employing known inputs using the EM-100 Controller Photo Beam Validation System, a robotically controlled vehicle representing a rodent and (2) biologic validation, employing groups of rats treated with the standard pharmacologic agents diazepam or D-amphetamine. The MotorMonitor's parameters that described the open-field activity of a subject were: basic movements, total distance, fine movements, x/y horizontal ambulations, rearing, and total rest time. These measurements were evaluated over a number of zones within each enclosure. System validation with the EM-100 Controller Photo Beam Validation System showed that all the parameters accurately and precisely measured what they were intended to measure, with the exception of fine movements and x/y ambulations. Biologic validation using the central nervous system depressant diazepam at 1, 2, or 5 mg/kg, i.p. produced the expected dose-dependent reduction in rat motor activity. In contrast, the central nervous system stimulant D-amphetamine produced the expected increases in rat motor activity at 0.1 and 1 mg/kg, i.p, demonstrating the specificity and sensitivity of the system. Taken together, these studies of the accuracy, precision, specificity, and sensitivity show the importance of both system and biologic validation in the evaluation of an automated open field motor activity system for use in a GLP compliant laboratory.

  12. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    International Nuclear Information System (INIS)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H.

    1990-01-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time

  13. The interaction of substituted benzamides with brain benzodiazepine binding sites in vitro.

    Science.gov (United States)

    Horton, R W; Lowther, S; Chivers, J; Jenner, P; Marsden, C D; Testa, B

    1988-08-01

    1. The interaction of substituted benzamides with brain benzodiazepine (BDZ) binding sites was examined by their ability to displace [3H]-flunitrazepam ([3H]-FNM) from specific binding sites in bovine cortical membranes in vitro. 2. Clebopride, Delagrange 2674, Delagrange 2335 and BRL 20627 displayed concentration-dependent displacement of [3H]-FNM with IC50 values of 73 nM, 132 nM, 7.7 microM and 5.9 microM, respectively. Other substituted benzamides including metoclopramide, sulpiride, tiapride, sultopride and cisapride were inactive at 10(-5) M. 3. Inhibition by clebopride and Delagrange 2674 of [3H]-FNM binding was apparently competitive and readily reversible. 4. In the presence of gamma-aminobutyric acid (GABA), the ability of diazepam and Delagrange 2674 to displace [3H]-Ro 15-1788 binding was increased 3.6 and 1.6 fold respectively, compared to the absence of GABA, while ethyl beta-carboline-3-carboxylate (beta CCE) and clebopride were less potent in the presence of GABA. 5. Diazepam was 30 fold less potent at displacing [3H]-Ro 15-1788 in membranes that had been photoaffinity labelled with FNM than in control membranes, whereas the potency of beta CCE did not differ. Clebopride and Delagrange 2674 showed a less than two fold loss of potency in photoaffinity labelled membranes. 6. The pattern of binding of clebopride and Delagrange 2674 in these in vitro tests is similar to that found previously with partial agonists or antagonists at BDZ binding sites. 7. Clebopride and Delagrange 2674 inhibited [3H]-FNM binding with similar potency in rat cerebellar and hippocampal membranes, suggesting they have no selectivity for BDZ1 and BDZ2 binding sites. 8. Clebopride and Delagrange 2674 are structurally dissimilar to other BDZ ligands and represent another chemical structure to probe brain BDZ binding sites.

  14. Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

    Science.gov (United States)

    López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

    2016-03-01

    Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. UPLC–MS/MS for the determination of azilsartan in beagle dog plasma and its application in a pharmacokinetics study

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    Cheng Gong

    2015-06-01

    Full Text Available The purpose of the study is to develop an ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS to determinate the concentration of azilsartan in the dog plasma. After precipitated by methanol, the plasma sample containing azilsartan and diazepam (internal standard, IS was determined by UPLC–MS/MS. The mobile phase consisted of acetonitrile-water was pumped at a flow rate of 0.3 ml/min in gradient elution. Kinetex 2.6 μ XB-C18 column (50 × 2.1 mm, 100 Å; Phenomenex, USA were used for LC separations. The column temperature was 30 °C and the injection volume was 5 μl. The electrospray ionization (ESI and multiple reaction monitoring (MRM were applied at the transitions of m/z 457 → 279 (azilsartan and m/z 285 → 193 (diazepam, respectively. The developed method was identified a good linearity over a concentration range of 2.5–5000 ng/ml. The lower limit of quantitation (LLOQ was 2.5 ng/ml. The intra-day and inter-day precision (relative standard deviation, RSD% were less than 10% and accuracy (relative error, RE % was less than 5% at three quality control levels. The extraction recovery of azilsartan at three quality control levels were 82.41 ± 0.68%, 98.66 ± 11.00%, 102.43 ± 0.82%. And the recovery for IS (100 ng/ml was 91.75 ± 0.54%. A validated UPLC–MS/MS method was firstly developed for the quantification of azilsartan in dog plasma and it was applied to the pharmacokinetics study.

  16. Genetic markers of a Munc13 protein family member, BAIAP3, are gender specifically associated with anxiety and benzodiazepine abuse in mice and humans.

    Science.gov (United States)

    Wojcik, Sonja M; Tantra, Martesa; Stepniak, Beata; Man, Kwun-Nok M; Müller-Ribbe, Katja; Begemann, Martin; Ju, Anes; Papiol, Sergi; Ronnenberg, Anja; Gurvich, Artem; Shin, Yong; Augustin, Iris; Brose, Nils; Ehrenreich, Hannelore

    2013-07-24

    Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders.

  17. Drug facilitated sexual assault: detection and stability of benzodiazepines in spiked drinks using gas chromatography-mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Lata Gautam

    Full Text Available Benzodiazepines are detected in a significant number of drug facilitated sexual assaults (DFSA. Whilst blood and urine from the victim are routinely analysed, due to the delay in reporting DFSA cases and the short half lives of most of these drugs in blood and urine, drug detection in such samples is problematic. Consideration of the drinks involved and analysis for drugs may start to address this. Here we have reconstructed the 'spiking' of three benzodiazepines (diazepam, flunitrazepam and temazepam into five drinks, an alcopop (flavoured alcoholic drink, a beer, a white wine, a spirit, and a fruit based non-alcoholic drink (J2O chosen as representative of those drinks commonly used by women in 16-24 year old age group. Using a validated GC-MS method for the simultaneous detection of these drugs in the drinks we have studied the storage stability of the benzodiazepines under two different storage conditions, uncontrolled room temperature and refrigerator (4°C over a 25 day period. All drugs could be detected in all beverages over this time period. Diazepam was found to be stable in all of the beverages, except the J2O, under both storage conditions. Flunitrazepam and temazepam were found not to be stable but were detectable (97% loss of temazepam and 39% loss of flunitrazepam from J2O. The recommendations from this study are that there should be a policy change and that drinks thought to be involved in DFSA cases should be collected and analysed wherever possible to support other evidence types.

  18. Management and complications of anaesthesia during balloon valvuloplasty for pulmonic stenosis in dogs: 39 cases (2000 to 2012).

    Science.gov (United States)

    Ramos, R V; Monteiro-Steagall, B P; Steagall, P V M

    2014-04-01

    The aim of this study was to report the management and complications of anaesthesia in dogs undergoing balloon valvuloplasty. A retrospective review of medical records of dogs that were diagnosed with pulmonic stenosis and undergoing balloon valvuloplasty between 2000 and 2012. Thirty-nine cases were identified (28 males and 11 females). Median (range) age and bodyweight was 6 (4 to 48) months and 11·5 (2·0 to 30·3) kg, respectively. The most commonly represented breeds included mixed breed (n = 7, 17·9%) and English bulldog (n = 6, 15·3%). Anaesthesia was induced most commonly with intravenous administration of ketamine-diazepam (n = 8, 20·5%), propofol-diazepam (n = 8, 20·5%), or propofol-midazolam-lidocaine (n = 6, 15·4%), and maintained with isoflurane in combination with fentanyl or lidocaine. Anaesthetic and surgery times (mean ± sd) were 268·5 ±54 minutes and 193·2 ±50 minutes, respectively. The most common intraoperative complications were hypotension (n = 19, 48·7%), bradycardia (n = 8, 20·5%) and desaturation (n = 7, 17·9%). Cardiac arrhythmias were observed in 21 (53·8%) dogs. Death occurred in one (2·6%) dog due to severe hypotension after ballooning followed by cardiac arrest. Successful anaesthesia can be performed in young dogs with pulmonic stenosis undergoing balloon valvuloplasty. Management of anaesthesia requires intense monitoring and immediate treatment of complications. Anaesthetic risk increases during ballooning and may result in cardiac arrest. © 2014 British Small Animal Veterinary Association.

  19. Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus.

    Science.gov (United States)

    Micale, Vincenzo; Stepan, Jens; Jurik, Angela; Pamplona, Fabricio A; Marsch, Rudolph; Drago, Filippo; Eder, Matthias; Wotjak, Carsten T

    2017-07-01

    The development of exaggerated avoidance behavior is largely responsible for the decreased quality of life in patients suffering from anxiety disorders. Studies using animal models have contributed to the understanding of the neural mechanisms underlying the acquisition of avoidance responses. However, much less is known about its extinction. Here we provide evidence in mice that learning about the safety of an environment (i.e., safety learning) rather than repeated execution of the avoided response in absence of negative consequences (i.e., response extinction) allowed the animals to overcome their avoidance behavior in a step-down avoidance task. This process was context-dependent and could be blocked by pharmacological (3 mg/kg, s.c.; SR141716) or genetic (lack of cannabinoid CB1 receptors in neurons expressing dopamine D1 receptors) inactivation of CB1 receptors. In turn, the endocannabinoid reuptake inhibitor AM404 (3 mg/kg, i.p.) facilitated safety learning in a CB1-dependent manner and attenuated the relapse of avoidance behavior 28 days after conditioning. Safety learning crucially depended on endocannabinoid signaling at level of the hippocampus, since intrahippocampal SR141716 treatment impaired, whereas AM404 facilitated safety learning. Other than AM404, treatment with diazepam (1 mg/kg, i.p.) impaired safety learning. Drug effects on behavior were directly mirrored by drug effects on evoked activity propagation through the hippocampal trisynaptic circuit in brain slices: As revealed by voltage-sensitive dye imaging, diazepam impaired whereas AM404 facilitated activity propagation to CA1 in a CB1-dependent manner. In line with this, systemic AM404 enhanced safety learning-induced expression of Egr1 at level of CA1. Together, our data render it likely that AM404 promotes safety learning by enhancing information flow through the trisynaptic circuit to CA1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures.

    Science.gov (United States)

    McQuaid, Kenneth R; Laine, Loren

    2008-05-01

    Numerous agents are available for moderate sedation in endoscopy. Our purpose was to compare efficacy, safety, and efficiency of agents used for moderate sedation in EGD or colonoscopy. Systematic review of computerized bibliographic databases for randomized trials of moderate sedation that compared 2 active regimens or 1 active regimen with placebo or no sedation. Unselected adults undergoing EGD or colonoscopy with a goal of moderate sedation. Sedation-related complications, patient assessments (satisfaction, pain, memory, willingness to repeat examination), physician assessments (satisfaction, level of sedation, patient cooperation, examination quality), and procedure-related efficiency outcomes (sedation, procedure, or recovery time). Thirty-six studies (N = 3918 patients) were included. Sedation improved patient satisfaction (relative risk [RR] = 2.29, range 1.16-4.53) and willingness to repeat EGD (RR = 1.25, range 1.13-1.38) versus no sedation. Midazolam provided superior patient satisfaction to diazepam (RR = 1.18, range 1.07-1.29) and less frequent memory of EGD (RR = 0.57, range 0.50-0.60) versus diazepam. Adverse events and patient/physician assessments were not significantly different for midazolam (with or without narcotics) versus propofol except for slightly less patient satisfaction (RR = 0.90, range 0.83-0.97) and more frequent memory (RR = 3.00, range 1.25-7.21) with midazolam plus narcotics. Procedure times were similar, but sedation and recovery times were shorter with propofol than midazolam-based regimens. Marked variability in design, regimens tested, and outcomes assessed; relatively poor methodologic quality (Jadad score sedation provides a high level of physician and patient satisfaction and a low risk of serious adverse events with all currently available agents. Midazolam-based regimens have longer sedation and recovery times than does propofol.

  1. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat

    Directory of Open Access Journals (Sweden)

    Alireza Komaki

    2014-07-01

    Full Text Available Introduction: Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP injection of cannabinoid CB1 receptor antagonist (AM251 in the presence of alpha-1 adrenergic antagonist (Prazosin on rat behavior in the EPM. Methods: In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg, Prazosin (0.3 mg/kg and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg. Results: Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Discussion: Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  2. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

    Science.gov (United States)

    Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

    2014-01-01

    Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  3. Anticonvulsant activity of the ethanolic extract of Punica granatum L. seed.

    Science.gov (United States)

    Mehrzadi, Saeed; Sadr, Samir; Hosseinzadeh, Azam; Gholamine, Babak; Shahbazi, Ali; FallahHuseini, Hasan; Ghaznavi, Habib

    2015-06-01

    Various morphological parts of pomegranate (Punica granatum L.) have extensively been used in the folk medicine to treat an array of human ailments. The aim of the present study is to demonstrate the anticonvulsant potential of the ethanolic extract of P. granatum L. seed in chemoconvulsant-induced seizures in mice. The anticonvulsant activity of the ethanolic extract was investigated in strychnine (STR)-induced and pentylenetetrazole (PTZ)-induced seizure models in mice. Diazepam was used as reference anticonvulsant drug. Ethanolic extract (150, 300, and 600 mg/kg per os, p.o.), diazepam (1 mg/kg intraperitoneally, i.p.), and distilled water (10 ml/kg, i.p.) were administered before induction of seizures by PTZ (60 mg/kg, i.p.) or STR (2.5 mg/kg, i.p.). The latent time before the onset of convulsions, the duration of convulsions, the percentage of seizure protection, and mortality rate were recorded. The seed ethanolic extract did not show any toxicity and did not protect the animals against seizures but demonstrated a significant increase in seizure latency at 300 and 600 mg/kg in both STR and PTZ seizure models (P < 0.001). It also showed a significant reduction in seizure duration at 300 mg/kg (P < 0.05) and 600 mg/kg (P < 0.001) in the STR seizure model and 600 mg/kg (P < 0.01) in the PTZ seizure model compared with the control group. Ethanol extract has dose-dependent anticonvulsant activity against STR- and PTZ-induced seizures. This activity might be due to its saponins, flavonoids, triterpenes, and alkaloids ingredients.

  4. Recent Advances in the Treatment of Organophosphorous Poisonings

    Directory of Open Access Journals (Sweden)

    Mahdi Balali-Mood

    2012-06-01

    Full Text Available Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of

  5. Recent Advances in the Treatment of Organophosphorous Poisonings

    Science.gov (United States)

    Balali-Mood, Mahdi; Saber, Hamidreza

    2012-01-01

    Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of organophosphorous poisoning

  6. Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials.

    Science.gov (United States)

    Premoli, Isabella; Király, Julia; Müller-Dahlhaus, Florian; Zipser, Carl M; Rossini, Pierre; Zrenner, Christoph; Ziemann, Ulf; Belardinelli, Paolo

    2018-03-15

    Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2-3 ms (short-interval intracortical inhibition, SICI) or ∼100 ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively. SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI. PpTMS-EEG was applied to the left motor cortex in 16 healthy subjects in a randomized, double-blind placebo-controlled crossover design, testing the effects of a single oral dose 20 mg of diazepam, a positive modulator at the GABAA receptor, vs. 50 mg of the GABAB receptor agonist baclofen on SICI of TEPs. We found significant SICI of the N100 and P180 TEPs prior to drug intake. Diazepam reduced SICI of the N100 TEP, while baclofen enhanced it. Compared to our previous ppTMS-EEG results on LICI, the SICI effects on TEPs, including their drug modulation, were largely analogous. Findings suggest a similar interaction of paired-pulse effects on TEPs irrespective of the interstimulus interval. Therefore, SICI and LICI as measured with TEPs cannot be directly derived from SICI and LICI measured with MEPs, but may offer novel insight into paired-pulse responses recorded directly from the brain rather than muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. First Chemical Evaluation and Toxicity of Casinga-cheirosa to Balb-c Male Mice

    Directory of Open Access Journals (Sweden)

    Dirce M. Estork

    2014-04-01

    Full Text Available Laetia suaveolens, known as “casinga-cheirosa”, crude extract EB719 has previously shown cytotoxic activity against prostate cancer and squamous cell carcinoma. For the first time, seven molecules were isolated from its apolar—α-tocopherol (1 and sitosterol (2—and polar—3-O-caffeoylquinic acid (3, 4-O-caffeoylquinic acid (4, 5-O-feruloylquinic acid (5, hyperoside (6, and isoquercitrin (7—fractions. Acute toxicity was determined in a two-stage experiment: (1 a reduced number of Balb-c male mice received 5000 mg/kg of EB719 to allow evaluation of general activity and other 27 parameters, plus death, up to the establishment of non-lethal dose (NLD, as well as lethal dose 50% (LD50; (2 NLD was administered and diazepam introduced as reference drug. EB719 showed LD50 = 178.0 mg/kg, and NLD 156.3 mg/kg. In stage one EB719 did not influence general activity, but provoked impairment in grasp reflexes, tail squeeze and breathing; piloerection and cyanosis were increased. In stage two, alterations occurred in auricular reflex, piloerection and breathing after diazepam administration, but not in response to EB719. Intestinal hemorrhage caused by local bleeding was observed after necropsy, and may be the main cause of animals’ death other than a systemic effect of the extract. Although the isolated compounds are biologically and pharmacologically active in both men and animal systems, it is premature to relate their occurrence in EB719 to the observed intestine hemorrhage in mice.

  8. Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

    Science.gov (United States)

    Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

    2017-02-01

    The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

  9. Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus.

    Science.gov (United States)

    Nakamura, Kensuke; Inokuchi, Ryota; Daidoji, Hiroaki; Naraba, Hiromu; Sonoo, Tomohiro; Hashimoto, Hideki; Tokunaga, Kurato; Hiruma, Takahiro; Doi, Kent; Morimura, Naoto

    2017-06-01

    Benzodiazepines are used as first-line treatments for status epilepticus. Fosphenytoin (FPHT) is recommended for second-line therapy; however, intravenous injection of levetiracetam (LEV) may also be effective against status epilepticus. Herein, we compared the efficacy and safety of LEV as a second-line treatment for status epilepticus with FPHT in Japanese patients.Patients with status epilepticus were selected from the database of the Emergency and Critical Care Center of Hitachi General Hospital. The subjects were patients whose status epilepticus was successfully stopped by diazepam, and in whom FPHT or LEV was administered after diazepam. As LEV injections recently became clinically available in Japan, the choice of drug was determined by the treatment period. Thus, 21 patients who were intravenously injected with LEV as a second-line therapy and 42 matched patients (historical controls) who were treated with FPHT (1:2) were selected.The subjects had a mean age of 64.0 ± 2.2 years, and included 48 males and 15 females. The status epilepticus control rates of the FPHT and LEV groups did not differ significantly (81.0% [34/42] vs 85.1% [18/21], respectively; P  =  .69). As for serious adverse events, a reduction in blood pressure was observed in the FPHT group, but not in the LEV group. The oral anticonvulsant switching rates of the 2 groups were similar, but the same-drug switching rates of the FPHT and LEV groups were 8.1% and 77.8%, respectively.The efficacy of intravenous LEV injections after status epilepticus was equivalent to that of FPHT, and the incidence of adverse events was lower in the LEV group. LEV is effective and safe at preventing recurrent seizures after status epilepticus following benzodiazepine treatment.

  10. Production of human metabolites by gastrointestinal bacteria as a potential source of post-mortem alteration of antemortem drug/metabolite concentrations.

    Science.gov (United States)

    Martindale, Stephanie M; Powers, Robert H; Bell, Suzanne C

    2015-01-01

    Previous studies have demonstrated that bacterial species are capable of transforming complex chemical substances. Several of these species, native to the human gastrointestinal tract, are active in postmortem decomposition. They have potential to cause biotransformations affecting compound-to-metabolite ratios within the human body, especially after death. Investigation of postmortem effects could supply valuable information, especially concerning compound identification and confirmation. The purpose of this research was to investigate the effects of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and to compare bacterial biotransformation products to those of human metabolism. A decrease in diazepam concentration between pre- and post-incubation was observed for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides fragilis (13.9-25.7%); however there was no corresponding increase in concentration for the monitored human metabolites. Flunitrazepam demonstrated a greater concentration loss when incubated with individual bacterial species as well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis, Clostridium perfringens, and mixed culture resulted in nearly complete conversion of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the majority of the conversion; however discrepancies in the mass balance of the reaction suggested the possibility of a minor metabolite that was not monitored in the current analysis. These experiments served as a pilot study and proof of concept that can be adapted and applied to a realm of possibilities. Ultimately, this methodology would be ideal to study compounds that are too toxic or lethal for animal and human metabolic investigations. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Occurrence and distribution of psychoactive compounds and their metabolites in the urban water cycle of Berlin (Germany).

    Science.gov (United States)

    Hass, Ulrike; Duennbier, Uwe; Massmann, Gudrun

    2012-11-15

    The occurrence and distribution of six psychoactive compounds (primidone, phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a metabolite of primidone (phenylethylmalonamide) were investigated in wastewater treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration site, raw and final drinking water, and in groundwater affected by former sewage irrigation. Primidone and its metabolite phenylethylmalonamide were found to be ubiquitous in environmental water samples in Berlin. Maximum concentrations of 0.87 and 0.42 μg/L, respectively, were encountered in WWTP effluents. Both compounds are apparently not removed when passaging through the different compartments of the water cycle and concentrations are only reduced by dilution. Phenobarbital was present at nearly every stage of the Berlin water cycle with the exception of raw and final drinking water. The highest concentrations of phenobarbital (up to 0.96 μg/L) were measured in groundwater influenced by former sewage irrigation. Oxazepam was only present in WWTP effluents and surface waters (up to 0.18 μg/L), while diazepam was not detected in any matrix. Due to their withdrawal from the German market years ago, the pharmaceuticals meprobamate and pyrithyldione were only found in sewage farm groundwater (up to 0.50 and 0.04 μg/L, respectively) and, in case of meprobamate, also in decade old bank filtrate (0.03 μg/L). Our results indicate a high persistence of some of the investigated compounds in the aquatic system. As a consequence, these pollutants may potentially reach drinking water resources via bank filtration if present in WWTP effluents and/or surface waters in partly closed water cycles such as Berlin's. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice

    Science.gov (United States)

    Smith, Kiersten S.; Engin, Elif; Meloni, Edward G.; Rudolph, Uwe

    2012-01-01

    GABAA receptor modulating drugs such as benzodiazepines (BZs) have been used to treat anxiety disorders for over five decades. In order to determine whether the same or different GABAA receptor subtypes are necessary for the anxiolytic-like action of BZs in unconditioned anxiety and conditioned fear models, we investigated the role of different GABAA receptor subtypes by challenging wild type, α1(H101R), α2(H101R) and α3(H126R) mice bred on the C57BL/6J background with diazepam or chlordiazepoxide in the elevated plus maze and the fear-potentiated startle paradigms. Both drugs significantly increased open arm exploration in the elevated plus maze in wild type, α1(H101R) and α3(H126R), but this effect was abolished in α2(H101R) mice; these were expected results based on previous published results. In contrast, while administration of diazepam and chlordiazepoxide significantly attenuated fear-potentiated startle (FPS) in wild type mice and α3(H126R) mice, the fear-reducing effects of these drugs were absent in both α1(H101R) and α2(H101R) point mutants, indicating that both α1- and α2-containing GABAA receptors are necessary for BZs to exert their effects on conditioned fear responses.. Our findings illustrate both an overlap and a divergence between the GABAA receptor subtype requirements for the impact of BZs, specifically that both α1- and α2-containing GABAA receptors are necessary for BZs to reduce conditioned fear whereas only α2-containing GABAA receptors are needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises the possibility that GABAergic pharmacological interventions for specific anxiety disorders can be differentially tailored. PMID:22465203

  13. Psicologia e odontopediatria: a contribuição da análise funcional do comportamento Psychology and pediatric dentistry: the contribution of behaviour functional analysis

    Directory of Open Access Journals (Sweden)

    Antonio Bento Alves de Moraes

    2004-01-01

    Full Text Available Objetivando analisar funcionalmente a atuação do odontopediatra, procedeu-se ao atendimento odontológico de 3 crianças não-colaboradoras, utilizando ansiolítico ou placebo. As sessões foram filmadas e registrou-se os eventos clínicos e comportamentais dos participantes, em intervalos de 15 segundos. Os resultados revelaram que a colaboração das crianças pode ser considerada condição estabelecedora para os comportamentos da profissional. O ansiolítico não demonstrou efeitos sobre o comportamento dos pacientes. "Direção", categoria comportamental predominantemente utilizada pela dentista, revelou-se eficaz na evocação de respostas de colaboração para 2 pacientes. Os dados expressam a contribuição da análise funcional do comportamento ao estudo da interação profissional-paciente em odontopediatria.The aim of this study was to carry out a functional description of the pediatric dentists' behavior concerning professional performance. Subjects were 3 uncooperative dental patients who were treated using placebo or diazepam. Dental sessions were videotaped. Procedures and behaviors were recorded in 15-second intervals. Results revealed that children's level of cooperative behavior may be a considered variable that affect professional behaviors. Diazepam was not effective. "Guidance" was predominantly used by the dentist and evoked cooperative behavior with two patients. The results express the contribution of behaviour functional analysis to the study of patterns of interaction between the dental practitioner and child patient.

  14. Anxiolytic-like effects of ursolic acid in mice.

    Science.gov (United States)

    Colla, André R S; Rosa, Julia M; Cunha, Mauricio P; Rodrigues, Ana Lúcia S

    2015-07-05

    Ursolic acid is a pentacyclic triterpenoid that possesses several biological and neuropharmacological effects including antidepressant-like activity. Anxiety disorders represent common and disability psychiatric conditions that are often associated with depressive symptoms. This work investigated the anxiolytic-like effects of ursolic acid administration in different behavioral paradigms that evaluate anxiety in mice: open field test, elevated plus maze test, light/dark box test and marble burying test. To this end, mice were administered with ursolic acid (0.1, 1 and 10mg/kg, p.o.) or diazepam (2mg/kg, p.o.), positive control, and submitted to the behavioral tests. The results show that ursolic acid (10mg/kg) elicited an anxiolytic-like effect observed by the increased total time in the center and decreased number of rearings responses in the open field test and an increased percentage of entries and total time spent in the open arms of elevated plus maze, similarly to diazepam. No significant effects of ursolic acid were shown in the light/dark box and marble burying test. These data indicate that ursolic acid exhibits anxiolytic-like effects in the open field and elevated plus maze test, but not in the light/dark box and marble burying test, showing the relevance of testing several behavioral paradigms in the evaluation of anxiolytic-like actions. Of note, the results extend the understanding on the effects of ursolic acid in the central nervous system and suggest that it may be a novel approach for the management of anxiety-related disorders. Copyright © 2015. Published by Elsevier B.V.

  15. Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys.

    Science.gov (United States)

    de la Garza, R; Johanson, C E

    1987-12-01

    Rhesus monkeys were trained to discriminate intragastrically administered d-amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock-avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence.

  16. Effect of root-extracts of Ficus benghalensis (Banyan) in memory, anxiety, muscle co-ordination and seizure in animal models.

    Science.gov (United States)

    Panday, Dipesh Raj; Rauniar, G P

    2016-11-03

    Ficus benghalensis L. (Banyan) is a commonly found tree in Eastern Nepal. Its different plant parts are used for various neurological ailments. This study was performed in mice to see its effects in various neuropharmacological parameters. Passive-avoidance (memory), Open-field (anxiety), Pentobarbital-induced Sleep potentiation (sleep), Rota-rod (muscle-co-ordination), Pentylenetetrazol-Induced and Maximal Electroshock Seizure Tests were performed. Sample size was calculated using G*Power 3.1.9.2. Aqueous root extracts (Soxhlet method) of Ficus benghalensis 100 mg/kg and 200 mg/kg with negative and positive controls were used. The experimental results were represented as Mean ± SD. P-value was set at test was appropriately used. Passive-avoidance test showed 200 mg/kg group spent significantly less. Time (0.00s + 0.00s) in shock-zone than Normal Saline-group (9.67 s + 14.36 s, P = 0.000) or Diazepam-group (41.07 s + 88.24 s, P = 0.000). Open-field test showed 200 mg/kg group spent significantly longer Time (24.77 s + 12.23 s) in central-square than either Normal Saline group (15.08 s + 6.81 s, P = 0.000) or Diazepam-group (15.32 s + 5.12 s, P = 0.000). In Rota-rod test, 200 mg/kg group fell off the rod significantly (P = 0.000) earlier (33.01 s + 43.61 s) than both Normal Saline (>120 s) and Diazepam (62.07 s + 43.83 s) PTZ model showed that 100 mg/kg significantly (P = 0.004) delayed seizure-onset (184.40s + 36.36 s) compared to Normal Saline (101.79 s + 22.81 s), however, in MES model 200 mg/kg significantly (P = 0.000) prolonged tonic hind-limb extension (17.57 s + 2.15 s) compared to Normal Saline (13.55 s + 2.75 s) or Phenytoin (00.00s + 00.00s). Aerial roots of Ficus benghalensis have memory-enhancing, anxiolytic, musclerelaxant, and seizure-modifying effect.

  17. Utilização de benzodiazepínicos por idosos de umaestratégia de saúde da família: implicações para enfermagem Utilización de benzodiazepinas en ancianos de una estrategia de salud familiar: implicaciones para enfermería The use of benzodiazepines in the elderly in a family health strategy: implications in

    Directory of Open Access Journals (Sweden)

    Paulo Celso Prado Telles Filho

    2011-09-01

    Full Text Available Os benzodiazepínicos são medicamentos que podem causar riscos aos idosos. Este estudo teve como objetivo verificar e analisar a prevalência da utilização de benzodiazepínicos por idosos cadastrados em uma Estratégia Saúde da Família de Diamantina - Minas Gerais. Trata-se de estudo descritivo, realizado com 27 idosos, de maio a julho de 2010, por meio de questionário semiestruturado. Utilizou-se a análise descritiva junto aos dados. Como resultados, destacaram-se a faixa etária de 71 a 75 anos (25,92%, gênero feminino (88,88% e, em relação à escolaridade, o primeiro grau incompleto (66,66%. Os medicamentos mais usados foram: Diazepam (37,03%, Clonazepam (25,92%, Bromazepam (18,51% e Alprazolam (11,11%. 88,90% dos entrevistados possuíam receita e 11,10% não a possuíam. Dentre os idosos que possuíam receita, 33,33% não a seguiam. Faz-se presente a necessidade de reorganizar o processo de trabalho na instituição investigada, de forma que se propicie uma adequação das prescrições e um seguimento mais eficaz destas.Las benzodiazepinas son medicamentos que pueden causar riesgos a los ancianos. Este estudio tuvo como objetivo verificar y analizar la prevalencia del uso de benzodiazepinas en ancianos registrados en una Estrategia de Salud Familiar de Diamantina - Minas Gerais - Brasil. Este es un estudio descriptivo con 27 ancianos, que ocurrió de mayo a julio de 2010, a través de cuestionario seme estructurado. El análisis descriptivo fue utilizado. Como resultados, se destacó la faja etaria de 71 a 75 años (25,92%, sexo femenino (88,88% y escolaridad primaria incompleta (66,66%. Los medicamentos más usados fueron: diazepam (37,03%, clonazepam (25,92%, bromazepam (18,51% y alprazolam (11,11%. El 88,9% de los entrevistados tienen receta médica, mientras 11,10% no la poseen. Entre los ancianos con receta, 33,3% no la siguen. Se hace necesario reorganizar el proceso de trabajo en la institución investigada, para hacer

  18. [Pharmacology of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (II). Sleep-inducing activity and effect on the motor system].

    Science.gov (United States)

    Yamamoto, K; Matsushita, A; Sawada, T; Naito, Y; Yoshimura, K; Takesue, H; Utsumi, S; Kawasaki, K; Hirono, S; Koshida, H

    1984-07-01

    The sleep-inducing activity and effect on the motor system of the 1H-1,2,4-triazolyl benzophenone derivative 450191-S were examined behaviorally, electroencephalographically and electro-physiologically with various species of animals and were compared with those of diazepam, nitrazepam, estazolam and triazolam. In the rhesus monkey, rabbit and rat with chronically indwelling brain electrodes, 0.6 to 3 mg/kg, p.o. of 450191-S caused a shorter latency of sleep onset, an increase of and a stable continuity of slow wave deep sleep (SWDS) with higher amplitude, and the appearance of clear spindle bursts in the slow wave light sleeping (SWLS) state with little muscle relaxation. Animals treated with nitrazepam and/or estazolam showed a smaller increase in SWDS and its unstable continuity with remarkable disturbance of gait. The doses needed to induce sleep in the rhesus monkey were 0.6 to 1 mg/kg p.o. for 450191-S, 3 mg/kg for nitrazepam, 1 mg/kg for estazolam and 0.3 mg/kg for triazolam. The cat treated with 450191-S showed the phenomena caused by benzodiazepines (BDZ), i.e., behavioral excitation and decrease of frequencies in the hippocampal theta waves. The suppressive effects of 450191-S on the EEG arousal reaction and/or blood pressure elevation induced by hypothalamic stimulation in the rabbit suggested that the inhibitory effects acted on the posterior hypothalamus to the limbic system. The inhibitory effect of 450191-S on the amygdaloid kindling in the rat was as potent as those of diazepam and nitrazepam. Successive daily oral administration of both 3 mg/kg of 450191-S and/or 3 to 6 mg/kg of nitrazepam for 15 days in the rabbit caused slight decrease of SWDS and increase of fast wave (REM) sleep (FWS). During the withdrawal period of both compounds, a slight but insignificant increase in the waking state was noticed for 1 to 2 days, but not a rebound increase of FWS. Intravenously administered 450191-S showed the same action as BDZ on the spinal reflex and the

  19. Morphological and Functional Analysis of Hepatocyte Spheroids Generated on Poly-HEMA-Treated Surfaces under the Influence of Fetal Calf Serum and Nonparenchymal Cells

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    Augustinus Bader

    2013-03-01

    .5. Disintegration of plasma membranes in both models was measured by lactate dehydrogenase (LDH release in both models. Additionally, diazepam was used as a substrate in drug metabolism studies to characterize the differences in the biotransformation potential with metabolite profiles in both models. It showed that the diazepam metabolism activities in the spheroid model is about 10-fold lower than the sandwich model. The poly-HEMA-based hepatocyte spheroid is a promising new platform towards hepatic tissue engineering leading to in vitro hepatic tissue formation.

  20. Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

    Science.gov (United States)

    Imran, Imran; Hillert, Markus H; Klein, Jochen

    2015-12-01

    The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by

  1. Evaluation of the Effect of Jobelyn® on Chemoconvulsants- Induced Seizure in Mice

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    Solomon Umukoro

    2013-04-01

    Full Text Available Introduction: Epilepsy is a common central nervous system (CNS disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn® (JB is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice. Methods: The animals received JB (5, 10 and 20 mg/kg, p.o 30 min before induction of convulsions with intraperitoneal (i.p. injection of picrotoxin (6 mg/kg, strychnine (2 mg/ kg and pentylenetetrazole (85 mg/kg respectively. Diazepam (2 mg/kg, p.o. was used as the reference drug. Anti-seizure activities were assessed based on the ability of test drugs to prevent convulsions, death or to delay the onset of seizures in mice. Results: JB (5, 10 and 20 mg/kg, p.o could only delay the onset of seizures induced by pentylenetetrazole (85 mg/kg, i.p. in mice. However, it did not offer any protection against seizure episodes, as it failed to prevent the animals, from exhibiting tonic-clonic convulsions caused by pentylenetetrazole (85 mg/kg, i.p., strychnine (2 mg/kg or picrotoxin (6 mg/kg, i.p.. On the other hand, diazepam (2 mg/kg, p.o., offered 100% protection against convulsive seizures, induced by pentylenetetrazole (85 mg/kg, i.p.. However, it failed to prevent seizures produced by strychnine (2 mg/kg, i.p. or picrotoxin (6 mg/kg, i.p.. Discussion: Our results suggest that JB could not prevent the examined chemoconvulsants-induced convulsions. However, its ability to delay the latency to seizures induced by pentylenetetrazole suggests that JB might be effective in the control of the seizure spread in epileptic brains.

  2. Sedatives for opiate withdrawal in newborn infants.

    Science.gov (United States)

    Osborn, David A; Jeffery, Heather E; Cole, Michael J

    2010-10-06

    Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings. Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. Each author assessed study quality and extracted data independently. Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group.One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure.In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study

  3. Opiate treatment for opiate withdrawal in newborn infants.

    Science.gov (United States)

    Osborn, David A; Jeffery, Heather E; Cole, Michael J

    2010-10-06

    Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. To assess the effectiveness and safety of using an opiate compared to a sedative or non-pharmacological treatment for treatment of NAS due to withdrawal from opiates. The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. Each author assessed study quality and extracted data independently. Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology.Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted.Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate.Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate.Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care

  4. Comparison of drugs used by nightclub patrons and criminal offenders in Oslo, Norway.

    Science.gov (United States)

    Gjerde, Hallvard; Nordfjærn, Trond; Bretteville-Jensen, Anne Line; Edland-Gryt, Marit; Furuhaugen, Håvard; Karinen, Ritva; Øiestad, Elisabeth L

    2016-08-01

    The aim of this study was to investigate psychoactive drug use among nightclub patrons by analysing samples of oral fluid and compare with findings in blood samples from criminal suspects. We hypothesized that the profile of illicit drug use among nightclub patrons is different from what we observe in those forensic cases. Research stations were established outside nine popular nightclubs with different profiles and patron-characteristics in downtown Oslo. Data and sample collection was conducted on Fridays and Saturdays in March and May 2014. Individuals and groups who entered defined recruitment zones from 23:00 to 03:30 were invited to participate in this voluntary and anonymous study. Oral fluid was collected using the Intercept Oral Fluid Sampling Device. Methanol was added to increase the recovery of cannabinoids from the device. Sample preparation was performed using liquid-liquid extraction with ethyl acetate/heptane (4:1) after adding internal standards, ammonium carbonate buffer pH 9.3 and Triton X100. The first 80 samples were analysed for 122 substances, which included psychoactive medicinal drugs, classical illicit drugs and new psychoactive substances (NPS). Based on the findings and discussions with police and customs authorities, the remaining oral fluid samples were analysed for 46 substances. Among the 500 samples collected during the study period, we found illicit drugs in 25.4% and medicinal drugs in 4.2% of the samples. The most prevalent substances were: cocaine 14.6%, THC 12.4%, amphetamine/methamphetamine 2.8%, diazepam 1.2% and clonazepam 1.0%. Various NPS were found in 1.4% of the samples. The prevalence of drugs in blood samples from criminal suspects were for cocaine 3.4%, THC 34.7%, amphetamine/methamphetamine 37.0%, diazepam 12.0%, and clonazepam 29.3%. Multi-drug use was more common among criminal suspects (41.3%) than among club patrons (6.8%). The results showed that the drug use pattern among nightclub patrons was substantially

  5. Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

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    David Fotsing

    2017-09-01

    , diazepam and in co-administration of the plant extract and diazepam treated rats. Moreover stressed rats showed significant changes in estrous cycle phases compared to vehicle control and these changes of the estrous cycle were less in the rats treated with G. dalenii compared to the negative control rats. G. dalenii extract showed antagonizing effects on the stress-induced reproductive, behavioral, and neurochemical changes. These effects could be related to the bioactive molecules and secondary metabolites like alkaloids and flavonoids in the plant.

  6. Hypnotic Effect of Portulaca oleracea L on Pentobarbital-Induced Sleep in Mice.

    Science.gov (United States)

    Hamedi, Shokouhsadat; Forouzanfar, Fatemeh; Rakhshandeh, Hasan; Arian, Amirali

    2018-03-08

    In Iranian Traditional Medicine, the herbs with cold and wet temperament can help to improve insomnia. Portulaca oleracea has cold and wet temperament, so the present study was carried out to investigate the sleep-prolonging effect of Portulaca oleracea. This work was an experimental study on mice which were randomly divided into these groups: saline (control); Diazepam:) positive control); hydro-alcoholic extract of Portulaca oleracea (12.5, 25, 50, 75 and 100 mg/kg) by Soxhlet apparatus and maceration; in the effective (dose25 mg/kg), different fractions of extract were tested. Ethyl acetate fraction (EAF:); n-Hexane fraction (n-HF); water fraction (WF). All the test compounds were injected intraperitoneally (IP) 30 minutes before pentobarbital administration (30 mg/kg). Duration and latency of pentobarbital-induced sleep were recorded. Also, LD50 of Portulaca oleracea extract was determined and the possible neurotoxicity of the extract was tested on neural PC12 cells. Besides, 30 min after administration of hydro alcoholic extract (HAE) motor coordination (rota-rod test) were assessed. HAE increased the duration of pentobarbital-induced sleep at doses of 25, 50, 75 and 100 mg/kg The hypnotic effect of HAE was comparable to that induced by diazepam. Similarly, WF, EAF, and n-HF at 25 mg/kg could increase sleep duration. The sleep latency was decreased by HAE and NHF but not by WF and EAF. The LD50 value for HAE was found to be 4.8 g/Kg. HAE and its fractions did not show neurotoxic effect in cultured PC12-cell line, also HAE did not affect the animals' performance on the rotarod test. The present data demonstrated that Portulaca oleracea potentiates sleeping behaviors. The main component (s) responsible for the hypnotic effects of this plant is most likely a non-polar agent (s) which is found in n-HF. Isolation of the active constituents may yield a novel sedative drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Guanidine hydrochloride denaturation of human serum albumin originates by local unfolding of some stable loops in domain III.

    Science.gov (United States)

    Ahmad, Basir; Ahmed, Md Zulfazal; Haq, Soghra Khatun; Khan, Rizwan Hasan

    2005-06-15

    The effect of guanidine hydrochloride (GnHCl) on the global stability of human serum albumin (HSA) has been studied by fluorescence and circular dichroism spectroscopic measurements. The differential stability of native conformation of three HSA domains were explored by using domain-specific ligands, hemin (domain I), chloroform (domain II), bilirubin (at domain I/domain II interface) and diazepam (domain III). GnHCl induced unfolding transition curves as monitored by probes for secondary and tertiary structures were cooperative but noncoincidental. A strong ANS binding to the protein was observed around 1.8 M GnHCl, suggesting existence of intermediate states in the unfolding pathway of HSA. A gradual decrease (in the GnHCl concentration range 0.0-1.8 M) in the binding of diazepam indicates that domain III is the most labile to GnHCl denaturation. A significant increase in the binding of bilirubin up to 1.4 M GnHCl and decrease thereafter leading to complete abolishment of bilirubin binding at around 2.0 M GnHCl suggest favorable rearrangement and separation of domains I and II at 1.4 and 2.0 M GnHCl concentration, respectively. Above 1.6 M GnHCl, decrease of the binding of hemin, a ligand for domain I, chloroform, which binds in domain II and lone tryptophanyl fluorescence (Trp-214 located in domain II) indicate that at higher concentration of GnHCl domains I and II start unfolding simultaneously but the stability of domain I (7.4 Kcal/mol) is much more than domain II (4.3 Kcal/mol). A pictorial model for the unfolding of HSA domains, consistent with all these results, has been formulated, suggesting that domain III is the most labile followed by domain II while domain I is the most stable. A molten globule like state of domain III around 1.8 M GnHCl has also been identified and characterized.

  8. Simultaneous determination of asperosaponin VI and its active metabolite hederagenin in rat plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in pharmacokinetic study.

    Science.gov (United States)

    Zhu, He; Ding, Li; Shakya, Shailendra; Qi, Xiemin; Hu, Linlin; Yang, Xiaolin; Yang, Zhonglin

    2011-11-15

    A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operated in the positive/negative electrospray ionization (ESI) switching mode has been developed and validated for the simultaneous determination of asperosaponin VI and its active metabolite hederagenin in rat plasma. After addition of internal standards diazepam (for asperosaponin VI) and glycyrrhetic acid (for hederagenin), the plasma sample was deproteinized with acetonitrile, and separated on a reversed phase C18 column with a mobile phase of methanol (solvent A)-0.05% glacial acetic acid containing 10 mM ammonium acetate and 30 μM sodium acetate (solvent B) using gradient elution. The detection of target compounds was done in multiple reaction monitoring (MRM) mode using a tandem mass spectrometry equipped with positive/negative ion-switching ESI source. At the first segment, the MRM detection was operated in the positive ESI mode using the transitions of m/z 951.5 ([M+Na](+))→347.1 for asperosaponin VI and m/z 285.1 ([M+H](+))→193.1 for diazepam for 4 min, then switched to the negative ESI mode using the transitions of m/z 471.3 ([M-H](-))→471.3 for hederagenin and m/z 469.4 ([M-H](-))→425.4 for glycyrrhetic acid, respectively. The sodiated molecular ion [M+Na](+) at m/z 951.5 was selected as the precursor ion for asperosaponin VI, since it provided better sensitivity compared to the deprotonated and protonated molecular ions. Sodium acetate was added to the mobile phase to make sure that abundant amount of the sodiated molecular ion of asperosaponin VI could be produced, and more stable and intensive mass response of the product ion could be obtained. For the detection of hederagenin, since all of the mass responses of the fragment ions were very weak, the deprotonated molecular ion [M-H](-)m/z 471.3 was employed as both the precursor ion and the product ion. But the collision energy was still used for the MRM, in order to eliminate the influences induced by the interference

  9. Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.

    Science.gov (United States)

    Dorado, P; López-Torres, E; Peñas-Lledó, E M; Martínez-Antón, J; Llerena, A

    2013-08-01

    Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first focal seizure with secondary generalization at 13 months of age. She initially received oral valproate treatment and three months later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age, she was admitted to the Emergency Department because of generalized convulsive Status Epilepticus needing to be immediately treated with rectal diazepam (0.5 mg kg(-1)), intravenous diazepam (0.3 mg kg(-1)), and intravenous phenytoin with an initial-loading dose of 15 mg kg(-1). However, two hours after the initial-loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and excessive sedation. Other potential causes of PTH toxicity were excluded such as drug interactions, decreased albumin or lab error. Therefore, to explain the neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms were analyzed. Initial plasma PTH levels were higher than expected (69 mg l(-1); normal range: 10-20 mg l(-1)), and the patient was homozygous for the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the 3435C and 1236C ABCB1 alleles. Present findings support the previously established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the increased risk to develop PTH toxicity owing to high plasma concentrations. Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient.

  10. Mortalidad por intoxicaciones agudas producidas con medicamentos: Cuba, 1995-1996

    Directory of Open Access Journals (Sweden)

    María Luisa González Valiente

    2000-04-01

    Full Text Available Se realizó un estudio descriptivo para determinar la incidencia de intoxicaciones agudas fatales medicamentosas en 1995 y 1996, y los principales factores de riesgo en la población cubana. Ocurrieron 314 defunciones para una tasa de 1,4 por 100 000 habitantes. En edades pediátricas el riesgo superior se encuentra en los menores de 1 a y en los adultos el riesgo aumenta al avanzar la edad, con una mayor afectación del sexo femenino. Las edades de mayor riesgo son a partir de 55 a en las mujeres y en los hombres después de 75 a. Los años de vida potencialmente perdidos fueron 7 430, con predominio de las mujeres (74 %. En los adultos predominaron las circunstancias voluntarias, en especial los suicidios con ingestión de psicofármacos; el diazepam y el fenobarbital se encuentran entre los más elegidos. En segundo término aparecen las reacciones adversas, producidas fundamentalmente por antibióticos, con predominio de las penicilinas. Por último, las circunstancias accidentales originadas por cardiotónicos. En los niños no existió diferencia estadística significativa en las diferentes circunstancias.We undertook a descriptive stuy to determine the incidence of fatal outcomes of acute drug poisoning in 1995 and 1996 and the main risk factors for the Cuban population. There were 314 deaths accounting for 1,4 death per 1000 pop. In pediatric ages, under 1 year-old infants are at the highest risk whereas risk for adults increases with age, being females the most affected ones. The most risky ages for women are from 55 years and over, and for men after 75 years of life. Potential years of life lost amounted to 7 430 with females predominating (74 %. Voluntary poisonings in adults prevailed spcially suicides from psychodrug-taking; diazepam and phenobarbital were the most used drugs for this end. Adverse drug effects was the second cause, which are mainly caused by antibiotics particularly penicilims. Lastly, accidental situations created

  11. Effects of serotonergic system on the sleeping time and EEG in rats

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    Alaei H

    2001-08-01

    Full Text Available The phenomenon of sleep is an active nervous and biologic rhythm, which is under influence of neurotransmitters of central nervous system. In this study, the influence of serotonergic system on sleeping time have been assessed by agonist-antagonist drugs using two methods of induction and non-induction behavioral and electrophysiology. The method used for measurement of total sleeing time was Angle method. For assessment of drugs impact on brain waves, after opening two holes in frontal and temporal regions, two non-polarized silvery electrodes were fixed in above regions and was connected to physiograph and computer by linkers for waves analysis. Injection intra-ventriculary is done by stereotax apparatus. Results indicate that diazepam (2.5 mg/kg increases sleeping time in two stages of induction and non-induction (P<0.01. 5-HTP (15, 45 mg/kg increases dose-dependence sleeping time. p-CPA (150, 300 mg/kg shows biphasic influence on sleeping time. The 300 mg/kg dose of p-CPA reduces sleeping time while 150 mg/kg dose inverts sleeping time (P<0.05. Interferential affects of drugs with (5-HTP 45 mg/kg and p-CPA (300 mg/kg doses are similar to control groups. Injection of 5-HTP inverts p-CPA affect. Intra-ventriculary Injection of 5-HTP in 150 µg/kg and 300 µg/kg doses, decreases frequency of delta waves and significantly increases the frequencies of other waves but conversely, 500 µg/kg decreases it. Due to findings of this study, interferential affects of agonist-antagonist of 5-HTP, can not invert p-CPA affect. Supported by GABA affects, diazepam induces its inhibitory affect in per-synaptic and post-synaptic membrane through ascending reticular both systems and blocking stimulation of brain cortical and limbic system. Affects of two other drugs on sleeping time and brain waves are probably caused by increment of released serotonin in pre-synaptic neurons. Although their interferential affects with other neurotransmitter system should be

  12. Comparação da anestesia geral e bloqueio do plexo cervical superficial em tireoidectomias parciais Comparison between general anesthesia and superficial cervical plexus block in partial thyroidectomies

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    Rui Celso Martins Mamede

    2008-02-01

    Full Text Available Tireoidectomia sob efeito de bloqueio do plexo cervical superficial (BPCS tem sofrido resistência. OBJETIVO: Comparar variáveis cirúrgicas e anestésicas, custos do tratamento e grau de satisfação de pacientes submetidos à hemitireoidectomia sob efeito de anestesia geral e BPCS. CASUÍSTICA E MÉTODOS: Foram 21 pacientes submetidos à anestesia geral (AG e outro tanto ao BPCS. Após sedação, no grupo com BPCS, usou-se marcaína com vasoconstritor, e quando necessário, lidocaína a 2% com vasoconstritor. Sedação intra-operatória com diazepam endovenoso e metoprolol para controle da PA e FC eram administradas quando necessário. Usou-se anestesia geral (AG segundo padronização do serviço. RESULTADOS: Foram significantes (pThyroidectomy under the effect of superficial cervical plexus block (SCPB has met resistance. AIM: to compare variables in patients submitted to hemithyroidectomy under the effect of general anesthesia (GA and SCPB. CASE REPORT AND METHODS: GA was used in 21 patients, and SCPB was used in another 21 patients. Following sedation, marcaine 0.5% with vasoconstrictor was used in the SCPB group. Intraoperative sedation with diazepam and metoprolol to control arterial pressure and cardiac frequency was given as needed. GA followed the standard method in the unit. RESULTS: We found significant results (p<0.05, Student’s t-test for surgery time (GA - 111.4 min; SCPB - 125.5 min, anesthesia time (GA - 154.1 min; SCPB - 488.6 min, time in the surgery room (GA - 15 min; SCPB - 1 min, treatment costs (GA - R$203.2; SCPB - R$87.4, presence of bradycardia (GA - 0; SCPB - 23.8% and laryngotracheal injury (GA - 51; SCPB - 0 %. We also found the following non-significant results: hospitalization time (GA - 17.3; SCPB - 15.1 hours; bleeding volume (GA - 41,9 g; SCPB - 47.6 g, size of the operative specimen (GA - 52.1 cm3; SCPB - 93.69 cm3 and patient satisfaction level (GA - 3.8; SCPB - 3.9. CONCLUSION: Although the incidence of

  13. Comparison of chemical restraint techniques in ostrich (Struthio camelus

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    R Ciboto

    2006-06-01

    Full Text Available Chemical restraint in ostriches is usually required for short-time interventions. Thus, this study established and evaluated intravenous anesthetics formulated from commonly used drugs in order to accomplish total restraint on this species and allow painful procedures to be performed. Thirty male and female ostriches weighing from 40 to 90 kg were randomly distributed into five groups. Animals in Groups I, II and III were given acepromazine (0.25 mg/kg i.m. and those in Groups IV and V were given xylazine (1.0 mg/kg i.m.. The following drugs were administered intravenously 15 to 20 min later: Group I - propofol (4.0 mg/kg, Groups II and IV - ketamine (5.0 mg/kg and diazepam (0.25 mg/kg, Groups III and V - tiletamine-zolazepam (3.0 mg/kg. All protocols have produced satisfactory results regarding total containment, muscular relaxation and maintenance of the evaluated parameters within a normal range.

  14. Volume-dependent hemodynamic effects of blood collection in canine donors - evaluation of 13% and 15% of total blood volume depletion

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    RUI R.F. FERREIRA

    2015-03-01

    Full Text Available Background: There is no consensus regarding the blood volume that could be safely donated by dogs, ranging from 11 to 25% of its total blood volume (TBV. No previous studies evaluated sedated donors.Aim: To evaluate the hemodynamic effects of blood collection from sedated and non-sedated dogs and to understand if such effects were volume-dependent.Materials and Methods: Fifty three donations of 13% of TBV and 20 donations of 15% TBV were performed in dogs sedated with diazepam and ketamine. Additionally, a total of 30 collections of 13% TBV and 20 collections of 15% TBV were performed in non-sedated dogs. Non-invasive arterial blood pressures and pulse rates were registered before and 15 min after donation. Results: Post-donation pulse rates increased significantly in both sedated groups, with higher differences in the 15% TBV collections. Systolic arterial pressures decreased significantly in these groups, while diastolic pressures increased significantly in 13% TBV donations. Non-sedated groups revealed a slight, but significant, SBP decrease. No clinical signs related to donations were registered.Conclusion: These results suggest that the collection of 15% TBV in sedated donors induces hemodynamic variations that may compromise the harmlessness of the procedure, while it seems to be a safe procedure in non-sedated dogs.

  15. Técnica para obtenção do aparelho geniturinário e dosagem do PSA (Prostate Specific Antigen no hamster sírio, Mesocricetus auratus Technique for collecting blood for PSA (Prostate Specific Antigen dosing and genitourinary system obtaining in syrian hamster, Mesocricetus auratus

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    Dimas José Araújo Vidigal

    2004-12-01

    Full Text Available Objetivo: Expor a técnica utilizada na colheita de sangue para dosagem do PSA ( Prostate Specific Antigen e retirada do aparelho geniturinário no hamster sírio, Mesocricetus auratus, e correlacionar os achados do PSA com as alterações histológicas dos anexos sexuais desse roedor. Métodos: Foram usados no experimento trinta (n= 30 Hamsters: dez (n=10 animais considerados jovens com idade média no momento da morte de 47,5 dias e vinte (n=20 animais considerados adultos com idade superior à um ano. Após serem anestesiados com cloridrato de quetamina e diazepam, foi colhido diretamente da veia cava, em nível de abdome superior, cerca de 1,5mL a 2,0mL de sangue para dosagem do PSA totalpelo método ELISA, com antígeno humano. Morriam após colheita do sangue. Constatado a morte do animal, fazia-se a laparotomia retirando-se em monobloco todo aparelho geniturinário para estudo histológico dos anexos sexuais. Correlacionou-se o PSA com as alterações histológicas encontradas. Resultados: Os animais após serem anestesiados com cloridrato de quetamina e diazepam intraperitonealmente, obteve-se um excelente plano anestésico, que possibilitou colher via trans-dérmica da veia cava inferior em abdome superior sangue para dosagem do PSA. O animal morria após colheita do sangue. Fazia-se a laparotomia, com retirada em monobloco do aparelho geniturinário para estudo histológico e comparação das alterações encontradas nos anexos sexuais com o PSA dosado. Entre os Hamsters Jovens a média do PSA encontrado foi de 0,252ng/mL. Desvio Padrão (DP = 0,36. Entre os Hamsters adultos esta média foi de 0,325 ng/mL, DP= 0,12 . Quando comparou-se as médias do PSA entre os dois grupos de jovens e adultos obteve-se p= 0,0427. Dentre os Hamsters jovens, três apresentaram PSA não detectado. A análise histológica mostrou que, entre os animais jovens, não foi identificada qualquer alteração das estruturas microscópicas da próstata, ves

  16. Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

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    Cho, Suengmok; Han, Daeseok; Kim, Seon-Bong; Yoon, Minseok; Yang, Hyejin; Jin, Young-Ho; Jo, Jinho; Yong, Hyeim; Lee, Sang-Hoon; Jeon, You-Jin; Shimizu, Makoto

    2012-01-01

    Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA(A)-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA(A)-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA(A)-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

  17. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    International Nuclear Information System (INIS)

    Mukhin, A.G.; Papadopoulos, V.; Costa, E.; Krueger, K.E.

    1989-01-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4'-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit 3 H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations

  18. Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L. Sw., Fabaceae, leaves

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    Dinesh Kumar

    2010-08-01

    Full Text Available In this study, ethanol extract of Caesalpinia pulcherrima (L. Sw., Fabaceae, leaves (CPEE was investigated for anticonvulsant effect against maximal electroshock (MES and pentylenetetrazole (PTZ induced seizures in rats and mice at dose levels 200 and 400 mg/kg, i.p. respectively. Diazepam (3 mg/kg, i.p. was used as a standard anticonvulsant drug for comparison. CPEE was found to be safe up to the dose of 4000 mg/kg in mice, when administered intraperitoneally. The extract at 400 mg/kg dose produced significant (p<0.01 anticonvulsant effect w.r.t. control against PTZ-induced clonic seizures. In MES-induced seizure model, there were no significant alterations in the onset as well as duration of hind limb extension seizures as compared to control at a dose of 200 mg/kg when administered intraperitoneally. However, the extract (CPEE, 400 mg/kg i.p. significantly (p<0.01 delayed the onset as well as decreased the duration of hind limb extension seizures (HLES as compared to control. However, the extract, CPEE, percentage protection of the animals was increased at higher dose (200 mg/kg in both the models. The results of the study suggest that ethanol extract of Caesalpinia pulcherrima (L. Sw. leaves possess anticonvulsant effect.

  19. [Benzodiazepine dependence and the risk of depression and anxiety disorders: seniors' health study].

    Science.gov (United States)

    Nkogho Mengue, P-G; Abdous, B; Berbiche, D; Preville, M; Voyer, P

    2014-06-01

    The objective of this study is to examine the relationship between benzodiazepine dependence and anxiety disorders and depression in people aged 65 years and over. We referred to the data from the study on the health of seniors, a survey of a representative sample of 707 benzodiazepine users living in the community in Quebec, Canada. Benzodiazepine dependence, anxiety disorders and depression were measured using self-reported questionnaires based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth revised edition. Seniors have consumed an average daily dose of 6.1±7.6mg diazepam equivalent to an average of 205±130 days. The prevalence of benzodiazepine dependence has been estimated at 9.5%. This dependence increases the risk of minor depression for females (relative risk [RR]=4.36, confidence interval 95% [95% CI]=1.19 to 15.99). The results of this study suggest that the use of benzodiazepines is far from being optimal among seniors in Quebec. The proportion of seniors who develop an addiction is important. The results illustrate the need to develop and implement programs to improve the quality of benzodiazepine use among this population. Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  20. Barriers to Seizure Management in Schools: Perceptions of School Nurses.

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    Terry, Debbie; Patel, Anup D; Cohen, Daniel M; Scherzer, Daniel; Kline, Jennifer

    2016-12-01

    The purpose of this study was to assess school nurses' perceptions of barriers to optimal management of seizures in schools. Eighty-three school nurses completed an electronic survey. Most agreed they felt confident they could identify a seizure (97.6%), give rectal diazepam (83.8%), and handle cluster seizures (67.1%), but fewer were confident they could give intranasal midazolam (63.3%), had specific information about a student's seizures (56.6%), or could swipe a vagus nerve stimulator magnet (47.4%). Nurses were more likely to be available at the time of a seizure in rural (17/20) (85%) versus suburban (21/34) (62%) or urban (8/25) (32%) schools (P = .001). School nurses are comfortable managing seizures in the school setting. However, a specific seizure plan for each child and education on intranasal midazolam and vagus nerve stimulator magnet use are needed. A barrier in urban schools is decreased availability of a nurse to identify seizures and administer treatment. © The Author(s) 2016.

  1. Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

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    Md. Josim Uddin

    2018-04-01

    Full Text Available Anisomeles indica (L. kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models.

  2. Nonmedical Abuse of Benzodiazepines in Opiate-Dependent Patients in Tehran, Iran

    Science.gov (United States)

    Babakhanian, Masuade; Sadeghi, Maliheh; Mansoori, Nader; Alam Mehrjerdi, Zahra; Tabatabai, Mahmood

    2012-01-01

    Objective: The purpose of the present preliminary study was to explore the prevalence of nonmedical abuse of benzodiazepines in a group of opiate-dependent patients who were on methadone maintenance treatment (MMT) program in outpatient clinics in the south-west of Tehran, Iran. Methods: 114 male and female opiate-dependent clients who met DSM.IV-TR criteria for opiate dependence with mean age 36.5 years participated in the study from 16 clinics and completed a self-report questionnaire on demographics and substance use details. Then the participants were interviewed on the details of nonmedical abuse of benzodiazepines. Results: The study findings indicated that the current nonmedical abuse of benzodiazepines was commonly prevalent among participants. The most common current benzodiazepines abused were alprazolam (100%) followed by chlordiazepoxide (96.5%), clonazepam (94.7%), diazepam (86.8%), lorazepam (79.8%) and oxazepam (73.7%) respectively. Depression (77%) and anxiety (72.8%) were frequently reported as the most important reasons associated with consuming benzodiazepines followed by problem in anger control (44.7%), suicide thought (12.3%), self-injury (7.9%), and suicide commitment (5.3%) respectively. Conclusion: Nonmedical abuse of benzodiazepines is an important problem among opiate addicts which should be considered in treatment interventions during MMT program. PMID:24644471

  3. Effect of methanol extract of Trigonella foenum-graecum L. seeds on anxiety, sedation and motor coordination.

    Science.gov (United States)

    Assad, Tahira; Khan, Rafeeq Alam

    2017-04-01

    Currently available anxiolytics cause numerous adverse effects and show craving and tolerance during long term treatment. Currently traditional medicines have been re-evaluated widely through work on various plant species. Numerous plants in traditional system show pharmacological activity with unlimited prospective for therapeutic use. Hence we planned to evaluate the effect of methanol extract of T. foenum-graecum L. seeds on anxiety, sedation and motor coordination in mice at different doses following 15 days of oral feeding. Effect on anxiety was assessed by Hole board test and Light and Dark transition models.Phenobarbitone induced sleeping time and Rota rod test were performed to assess effect on sedation and motor coordination. In Hole board test, T. foenum-graecum L. seeds decreased the number of head dips in mice at all the three doses. In Light and Dark transition model, T. foenum-graecum L. seeds increased the period spent in the light box and the number of moves among the two compartments at 100 and 200 mg/kg as compared to control animals. In phenobarbitone induced sleeping time, T. foenum-graecum L. seeds did not reveal any sedative effect. In Rota rod test, extract exhibited significant skeletal muscle relaxant effect at 200 mg/kg (at 90 min) as compared to the control animals. Results of our study shows significant antianxiety effects of T. foenum-graecum L. seeds and may also recommend improved adverse effect profile as compared to diazepam.

  4. Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats

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    Daniela I Beiderbeck

    2014-05-01

    Full Text Available Neuropeptide S (NPS exerts robust anxiolytic and memory enhancing effects, but only in a non-social context. In order to study whether NPS affects aggressive behavior we used Wistar rats bred for low (LAB and high (HAB levels of innate anxiety-related behaviour, respectively, which were both described to display increased levels of aggression compared with Wistar rats not selectively bred for anxiety (NAB. Male LAB, HAB and NAB rats were tested for aggressive behavior towards a male intruder rat within their home cage (10 min, resident-intruder [RI] test. Intracerebroventricular (icv infusion of NPS (1 nmol significantly reduced inter-male aggression in LAB rats, and tended to reduce aggression in HAB and NAB males. However, local infusion of NPS (0.2 or 0.1 nmol NPS into either the nucleus accumbens or the lateral hypothalamus did not influence aggressive behavior. Social investigation in the RI test and general social motivation assessed in the social preference paradigm were not altered by icv NPS. The anti-aggressive effect of NPS is most likely not causally linked to its anxiolytic properties, as intraperitoneal administration of the anxiogenic drug pentylenetetrazole decreased aggression in LAB rats whereas the anxiolytic drug diazepam did not affect aggression of HAB rats. Thus, although NPS has so far only been shown to exert effects on non-social behaviors, our results are the first demonstration of anti-aggressive effects of NPS in male rats.

  5. Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2008-08-21

    Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

  6. Determination of Four Anti-epileptic Drugs in Plasma Using Ultra Performance Liquid Chromatography with Mass Detection Technique.

    Science.gov (United States)

    Hassib, Sonia T; Hashem, Hanaa M A; Mahrouse, Marianne A; Mostafa, Eman A

    2018-04-10

    Status epilepticus (SE) is considered the second most frequent neurologic emergency. Its therapeutic management is performed using sequential anti-epileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four anti-epileptic drugs in human plasma. Their separation and quantification were achieved using ultra performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285→193 for DIA, m/z 326→291 for MID, m/z 253→182 for PHT and m/z 237→194, 237→192 for IS. For the fourth drug (PB), molecular ion peak of PB [M+H] + at m/z 233 was used for its quantitation. The method was linear over concentration ranges of 5-500 ng/ml for DIA and MID and 0.25-20 μg/ml for PHT and PB, respectively. Bio-analytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies. This article is protected by copyright. All rights reserved.

  7. Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

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    Paolo Bellavite

    2012-01-01

    Full Text Available Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s. in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C, a placebo (solvent vehicle, and the reference drugs diazepam (1 mg/kg body weight or buspirone (5 mg/kg body weight were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD choice test and the open-field (OF exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization.

  8. Isolation of bergenin from the root bark of Securinega virosa and evaluation of its potential sleep promoting effect.

    Science.gov (United States)

    Magaji, Mohammed Garba; Musa, Aliyu Muhammad; Abdullahi, Musa Ismail; Ya'u, Jamilu; Hussaini, Isa Marte

    2015-01-01

    Securinega virosa Roxb (Ex Willd) Baill (Euphorbaiceae) root bark has been reportedly used in African traditional medicine in the management of mental illnesses. Previously, the sleep-inducing potential of the crude methanol root bark of Securinega virosa extract and its butanol fraction have been reported. The study aimed to isolate and characterize the bioactive constituent that may be responsible for the sleep inducing property of the root of the plant. The phytochemical investigation of the S. virosa root bark was carried out leading to the isolation of a compound from the butanol-soluble fraction of the methanol extract. The structure of the compound was elucidated on the basis of its spectral data, including IR, 1D and 2D NMR, mass spectrometry as well as X-ray diffraction analysis. The compound was investigated for sleep-inducing potential using diazepam-induced sleeping time test and beam walking assay in mice. This is the first report on the isolation of bergenin from the root of the plant. It significantly decreased the mean onset of sleep [F (2, 15) =7.167; ptested. Bergenin isolated from the root bark of S. virosa possesses sleep-inducing property and could be partly responsible for the sedative potential of the root of S. virosa.

  9. Drug eruptions from phenylbutazone in Jamu.

    Science.gov (United States)

    Giam, Y C; Tham, S N; Tan, T; Lim, A

    1986-01-01

    Drug eruptions from indeginous medicine is often difficult to diagnosis and confirm. It is known that a number of these now supplied by bomohs and Chinese sinsehs contain known drugs and are dispensed as tablets and capsules. We report 3 cases of adverse drug eruption to "Jamu", a Malay herb. A particular brand, "Jamu Indonesia, Toko Air Pancur", from Johor Bahru, Malaysia, is especially recommended for "sakit pinggang" or backache. The cases occurred between January and February 1985, and all had taken brown kidney shaped tablets. The adverse reactions were moderately severe. Two had erythroderma with hepatitis, and one, Steven Johnson Syndrome. Analysis of this jamu for analgesics led to the discovery of adulteration with phenylbutazone and diazepam. Records from local cases from 1974-1984 showed that 8 other patients, all Chinese had adverse cutaneous eruptions from phenylbutazone, oxybutazone and propyphenazone. The skin manifestations were erythroderma (2 cases), vasculitis (2 cases) and toxic epidermal necrolysis (4 cases). Those with toxic epidermal necrolysis had 100% mortality.

  10. Degradation and intermediates of diclofenac as instructive example for decomposition of recalcitrant pharmaceuticals by hydroxyl radicals generated with pulsed corona plasma in water.

    Science.gov (United States)

    Banaschik, Robert; Jablonowski, Helena; Bednarski, Patrick J; Kolb, Juergen F

    2018-01-15

    Seven recalcitrant pharmaceutical residues (diclofenac, 17α-ethinylestradiol, carbamazepine, ibuprofen, trimethoprim, diazepam, diatrizoate) were decomposed by pulsed corona plasma generated directly in water. The detailed degradation pathway was investigated for diclofenac and 21 intermediates could be identified in the degradation cascade. Hydroxyl radicals have been found primarily responsible for decomposition steps. By spin trap enhanced electron paramagnetic resonance spectroscopy (EPR), OH-adducts and superoxide anion radical adducts were detected and could be distinguished applying BMPO as a spin trap. The increase of concentrations of adducts follows qualitatively the increase of hydrogen peroxide concentrations. Hydrogen peroxide is eventually consumed in Fenton-like processes but the concentration is continuously increasing to about 2mM for a plasma treatment of 70min. Degradation of diclofenac is inversely following hydrogen peroxide concentrations. No qualitative differences between byproducts formed during plasma treatment or due to degradation via Fenton-induced processes were observed. Findings on degradation kinetics of diclofenac provide an instructive understanding of decomposition rates for recalcitrant pharmaceuticals with respect to their chemical structure. Accordingly, conclusions can be drawn for further development and a first risk assessment of the method which can also be applied towards other AOPs that rely on the generation of hydroxyl radicals. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala

    Directory of Open Access Journals (Sweden)

    Iandra Holzmann

    2011-01-01

    Full Text Available There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP, known as “Valeriana del monte”, and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM, forced swimming (FST, strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5% and time spent (44.7% in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.

  12. Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis.

    Science.gov (United States)

    Chan, Wui Ling; Wood, David M; Hudson, Simon; Dargan, Paul I

    2013-09-01

    There is evidence from around Europe of the availability and use of 6-(2-aminopropyl)benzofuran (6-APB) as a recreational drug. However, there is currently limited information on the acute toxicity of this compound. We describe here a case of acute toxicity associated with recreational use of legal high (6-APB) and cannabis, in which the comprehensive toxicological analysis confirmed the presence of a significant amount of 6-APB together with metabolites of both tetrahydrocannabinol and the synthetic cannabinoid receptor agonist (JWH-122). A 21-year-old gentleman with no previous medical and psychiatric history was brought to the emergency department (ED) after he had developed agitation and paranoid behaviour following the use of 6-APB purchased over the Internet. There was no obvious medical cause for his acute psychosis. He required diazepam to control his agitation and was subsequently transferred to a psychiatric hospital for ongoing management of his psychosis. Toxicological screening of a urine sample collected after presentation to the ED detected 6-APB, with an estimated urinary concentration of 2,000 ng/ml; other drugs were also detected, but at lower concentrations including metabolites of the synthetic cannabinoid receptor agonist JWH-122 and tetrahydrocannabinol. This is the first case of analytically confirmed acute toxicity associated with the detection of 6-APB which will provide some information on acute toxicity of this drug to help clinicians with the management of such patients and legislative authorities in their consideration for the need of its control.

  13. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Science.gov (United States)

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  14. Effects of chronic mild stress on the development of drug dependence in rats.

    Science.gov (United States)

    Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

    2014-09-01

    There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

  15. Methadone-induced delayed posthypoxic encephalopathy: clinical, radiological, and pathological findings.

    Science.gov (United States)

    Mittal, Manoj; Wang, Yunxia; Reeves, Alan; Newell, Kathy

    2010-01-01

    Objective. To describe the clinical, radiological and pathological findings in a patient with methadone-induced delayed posthypoxic encephalopathy (DPHE). Case Report. A Thirty-eight-year-old man was found unconscious for an unknown duration after methadone and diazepam ingestion. His initial vitals were temperature 104 degree Fahrenheit, heart rate 148/minute, respiratory rate 50/minute, and blood pressure 107/72 mmhg. He developed renal failure, rhabdomyolysis, and elevated liver enzymes which resolved completely in 6 days. After 2 weeks from discharge he had progressive deterioration of his cognitive, behavioral and neurological function. Brain MRI showed diffuse abnormal T2 signal in the corona radiata, centrum semiovale, and subcortical white matter throughout all lobes. Extensive work up was negative for any metabolic, infectious or autoimmune disorder. Brain biopsy showed significant axonal injury in the white matter. He was treated successfully with combination of steroids and antioxidants. Follow up at 2 year showed no residual deficits. Conclusion. Our observation suggests that patients on methadone therapy should be monitored for any neurological or psychiatric symptoms, and in suspected cases MRI brain may help to make the diagnosis of DPHE. A trial of steroids and antioxidants may be considered in these patients.

  16. Methadone-Induced Delayed Posthypoxic Encephalopathy: Clinical, Radiological, and Pathological Findings

    Directory of Open Access Journals (Sweden)

    Manoj Mittal

    2010-01-01

    Full Text Available Objective. To describe the clinical, radiological and pathological findings in a patient with methadone-induced delayed posthypoxic encephalopathy (DPHE. Case Report. A Thirty-eight-year-old man was found unconscious for an unknown duration after methadone and diazepam ingestion. His initial vitals were temperature 104 degree Fahrenheit, heart rate 148/minute, respiratory rate 50/minute, and blood pressure 107/72 mmhg. He developed renal failure, rhabdomyolysis, and elevated liver enzymes which resolved completely in 6 days. After 2 weeks from discharge he had progressive deterioration of his cognitive, behavioral and neurological function. Brain MRI showed diffuse abnormal T2 signal in the corona radiata, centrum semiovale, and subcortical white matter throughout all lobes. Extensive work up was negative for any metabolic, infectious or autoimmune disorder. Brain biopsy showed significant axonal injury in the white matter. He was treated successfully with combination of steroids and antioxidants. Follow up at 2 year showed no residual deficits. Conclusion. Our observation suggests that patients on methadone therapy should be monitored for any neurological or psychiatric symptoms, and in suspected cases MRI brain may help to make the diagnosis of DPHE. A trial of steroids and antioxidants may be considered in these patients.

  17. Evaluation of Blalock-Taussig shunts using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Okajima, Yoshitomo; Tashima, Kazuyuki; Terai, Masaru; Niwa, Koichirou.

    1988-01-01

    Four patients aged 3 to 18 months (mean 13 months) with a total of five Blalock-Taussig shunts (BT shunts; two were original BT shunts and three were modified BT shunts using GOLASKI grafts) underwent evaluation by ECG-gated magnetic resonance imaging. There were two cases with pulmonary atresia with intact ventricular septum, one with double outlet right ventricle with pulmonary stenosis and one with tetralogy of Fallot with pulmonary atresia who underwent bilateral BT shunts. At the time of study, an auscultory shunt murmur was audible in all patients. The magnetic resonance images were obtained with a Picker International Vista MR with a superconducting magnet operating at 0.5 Tesla. A spin echo sequence (echo time 40 msec) was used. All patients were placed within a 30 cm head coil radio antenna and sedated with chloral hydrate or diazepam. Four of 5 shunts were imaged on both coronal sections and sagittal sections during enddiastole. And there was no signal within the grafts. When the velocity of blood flow is beyond the cutoff velocity, the signal intensity of flowing blood is near background level. So we judged these grafts were patient. Our results showed that MRI was a very useful noninvasive method for evaluation of BT shunts. (author)

  18. Evaluation of Blalock-Taussig shunts using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Okajima, Yoshitomo; Tashima, Kazuyuki; Terai, Masaru; Niwa, Koichirou.

    1988-10-01

    Four patients aged 3 to 18 months (mean 13 months) with a total of five Blalock-Taussig shunts (BT shunts; two were original BT shunts and three were modified BT shunts using GOLASKI grafts) underwent evaluation by ECG-gated magnetic resonance imaging. There were two cases with pulmonary atresia with intact ventricular septum, one with double outlet right ventricle with pulmonary stenosis and one with tetralogy of Fallot with pulmonary atresia who underwent bilateral BT shunts. At the time of study, an auscultory shunt murmur was audible in all patients. The magnetic resonance images were obtained with a Picker International Vista MR with a superconducting magnet operating at 0.5 Tesla. A spin echo sequence (echo time 40 msec) was used. All patients were placed within a 30 cm head coil radio antenna and sedated with chloral hydrate or diazepam. Four of 5 shunts were imaged on both coronal sections and sagittal sections during enddiastole. And there was no signal within the grafts. When the velocity of blood flow is beyond the cutoff velocity, the signal intensity of flowing blood is near background level. So we judged these grafts were patient. Our results showed that MRI was a very useful noninvasive method for evaluation of BT shunts.

  19. In Vivo Antistress and Antioxidant Effects of Fermented and Germinated Mung Bean

    Directory of Open Access Journals (Sweden)

    Swee Keong Yeap

    2014-01-01

    Full Text Available Mung bean has been traditionally used to alleviate heat stress. This effect may be contributed by the presence of flavonoids and γ-aminobutyric acid (GABA. On the other hand, fermentation and germination have been practised to enhance the nutritional and antioxidant properties of certain food products. The main focus of current study was to compare the a