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Sample records for flurazepam

  1. Evaluation of flurazepam and placebo on sleep disorders in childhood

    Directory of Open Access Journals (Sweden)

    Rubens Reimão

    1982-03-01

    Full Text Available The clinically observed results in 40 patients, from 1 to 15 years old, presenting sleep disturbances, in a comparative and statistically approached study of flurazepam 15mg daily against placebo, are reported. Placebo was administered, followed by the drug, during 14 days each. The chief complaints were sleepwalking, sleep-talking, sleep terror, sleep-related bruxism, sleep-related headbanging, insomnia and excessive movements during sleep. A significant effect of flurazepam on sleepwalking, sleep-talking, bruxism, sleep terror and excessive movement during sleep, was observed. The insomniac and headbanging patients were not enough for statistical analysis. Flurazepam side effects were excessive drowsiness during daytime in 3 cases; irritability, 3 cases; nausea and vomiting, 2 cases, and were not correlated with age. Placebo side effects were similar, except for nausea and vomiting which were not observed. It was necessary to discontinue flurazepam in 2 cases, because of excessive drowsiness during daytime, which did not improve when reducing the dose.

  2. Evaluation of flurazepam and placebo on sleep disorders in childhood

    OpenAIRE

    Reimão, Rubens; Lefévre, Antonio B.

    1982-01-01

    The clinically observed results in 40 patients, from 1 to 15 years old, presenting sleep disturbances, in a comparative and statistically approached study of flurazepam 15mg daily against placebo, are reported. Placebo was administered, followed by the drug, during 14 days each. The chief complaints were sleepwalking, sleep-talking, sleep terror, sleep-related bruxism, sleep-related headbanging, insomnia and excessive movements during sleep. A significant effect of flurazepam on sleepwalking,...

  3. Evaluation of possible interaction among drugs contemplated for use during manned space flights. Part 1: Summary from progress report dated 31 October 1973. Part 2: Progress report for the period November 1973 to June 1974

    Science.gov (United States)

    1974-01-01

    Possible interactions among drugs contemplated for use during manned spaceflights have been studied in several animal species. The following seven drugs were investigated: nitrofurantoin, chloral hydrate, hexobarbital, phenobarbital, flurazepam, diphenoxylate, and phenazopyridine. Particular combinations included: chloral hydrate, hexobarbital or flurazepam with nitrofurantoin; phenobarbital or flurazepam with phenazopyridine; and diphenoxylate with two dose formulations of nitrofurantoin. The mechanism of action and an explanation of the interaction between diphenoxylate and nitrofurantoin still remains unclear. In man, the interaction does not appear to be significant, affecting only two subjects out of six and with only one dose formulation (Furadantin).

  4. Evaluation of possible interaction among drugs contemplated for use during manned space flights

    Science.gov (United States)

    1973-01-01

    Possible interactions among drugs contemplated for use during manned spaceflights have been studied in several animal species. The following seven drugs were investigated: nitrofurantoin, chloral hydrate, hexobarbital, phenobarbital, flurazepam, diphenoxylate, and phenazopyridine. Particular combinations included: chloral hydrate, hexabarbital or flurazepam with nitrofurantoin; phenobarbital or flurazepam with phenazopyridine; and diphenoxylate with two does formulations of nitrofurantoin. Studies were carried out in several species to determine whether induction of liver microsomal enzymes would increase the tendency of phenazopyridine to produce methemoglobin in vivo. Animals were premedicated with phenobarbital, a known inducer of azoreductase, and in a separate experiment with flurazepam, before administration of phenazopyridine. Methemoglobin production was determined in each animal after receiving phenazopyridine. No evidence was found for increased production of methemoglobin in the rat, dog, or rabbit that could be attributed to increased amounts of microsomal enzymes.

  5. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Vol. 47/No. RR-4.

    Science.gov (United States)

    1998-04-17

    suppression. • The following drugs may increase ZDV concentration (and therefore potential toxicity): probenecid, atovaquone, methadone , valproic acid...antihistamines (e.g., astemizole orterfenadine); certain cardiac drugs (e.g., amiodarone, bepridil hydrochloride , encainide hydrochlo- ride, flecainide...flurazepam hydrochloride , midazolam, triazolam, or zolpidem tartrate); certain psychotropic drugs (e.g., bupropion hydrochloride , clozapine, or pimoz

  6. Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines.

    Science.gov (United States)

    Blednov, Yuri A; Benavidez, Jillian M; Black, Mendy; Mayfield, Jody; Harris, R Adron

    2015-08-01

    Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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.

  8. GABA/benzodiazepine receptor complex in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.

    1987-01-01

    LS mice are more sensitive to benzodiazepine-induced anesthesia; however, the two lines do not differ in their hypothermic response to flurazepam. SS mice are more resistant to 3-mercaptopropionic acid-induced seizures and more sensitive to the anticonvulsant effects of benzodiazepines. The various correlates of GABA and benzodiazepine actions probably are the results of different mechanisms of action and/or differential regional control. Bicuculline competition for 3 H-GABA binding sites is greater in SS cerebellar tissue and 3 H-flunitrazepam binding is greater in the mid-brain region of LS mice. GABA enhancement of 3 H-flunitrazepma binding is greater in SS mice. Ethanol also enhances 3 H-flunitrazepam binding and increases the levels of 3 H-flunitrazepam binding above those observed for GABA. Using correlational techniques on data from LS and SS mice and several inbred mouse strains, it was demonstrated that a positive relationship exists between the degree of receptor coupling within the GABA receptor complex and the degree of resistance to seizures

  9. Absorbance detector for high performance liquid chromatography based on a deep-UV light-emitting diode at 235nm.

    Science.gov (United States)

    da Silveira Petruci, João Flavio; Liebetanz, Michael G; Cardoso, Arnaldo Alves; Hauser, Peter C

    2017-08-25

    In this communication, we describe a flow-through optical absorption detector for HPLC using for the first time a deep-UV light-emitting diode with an emission band at 235nm as light source. The detector is also comprised of a UV-sensitive photodiode positioned to enable measurement of radiation through a flow-through cuvette with round aperture of 1mm diameter and optical path length of 10mm, and a second one positioned as reference photodiode; a beam splitter and a power supply. The absorbance was measured and related to the analyte concentration by emulating the Lambert-Beer law with a log-ratio amplifier circuitry. This detector showed noise levels of 0.30mAU, which is comparable with our previous LED-based detectors employing LEDs at 280 and 255nm. The detector was coupled to a HPLC system and successfully evaluated for the determination of the anti-diabetic drugs pioglitazone and glimepiride in an isocratic separation and the benzodiazepines flurazepam, oxazepam and clobazam in a gradient elution. Good linearities (r>0.99), a precision better than 0.85% and limits of detection at sub-ppm levels were achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Development and validation of an EI-GC-MS method for the determination of benzodiazepine drugs and their metabolites in blood: applications in clinical and forensic toxicology.

    Science.gov (United States)

    Papoutsis, Ioannis I; Athanaselis, Sotirios A; Nikolaou, Panagiota D; Pistos, Constantinos M; Spiliopoulou, Chara A; Maravelias, Constantinos P

    2010-08-01

    Benzodiazepines are used widely in daily clinical practice, due to their multiple pharmacological actions. The frequent problems associated with the wide use of benzodiazepines, as well as the multiple incidents of poisonings, led to the necessity for the development of a precise, sensitive and rapid method for the simultaneous determination of the 23 most commonly used benzodiazepines (diazepam, nordiazepam, oxazepam, bromazepam, alprazolam, lorazepam, medazepam, flurazepam, fludiazepam, tetrazepam, chlordiazepoxide, clobazam, midazolam, flunitrazepam, 7-amino-flunitrazepam, triazolam, prazepam, nimetazepam, nitrazepam, temazepam, lormetazepam, clonazepam, camazepam) in blood. A gas chromatographic method combined with mass spectrometric detection was developed, optimized and validated for the determination of the above substances. This method includes liquid-liquid extraction with chloroform at pH 9 and two stages of derivatization using tetramethylammonium hydroxide and propyliodide (propylation), as well as a mixture of triethylamine:propionic anhydride (propionylation). The recoveries were higher than 74% for all the benzodiazepines. The calibration curves were linear within the dynamic range of each benzodiazepine with a correlation coefficient higher than 0.9981. The limits of detection and quantification for each analyte were statistically calculated from the relative calibration curves. Accuracy and precision were also calculated and were found to be less than 8.5% and 11.1%, respectively. The developed method was successfully applied for the investigation of both forensic and clinical toxicological cases of accidental and suicidal poisoning. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  11. Quantitative analysis of benzodiazepines in vitreous humor by high-performance liquid chromatography

    Science.gov (United States)

    Bazmi, Elham; Behnoush, Behnam; Akhgari, Maryam; Bahmanabadi, Leila

    2016-01-01

    Objective: Benzodiazepines are frequently screened drugs in emergency toxicology, drugs of abuse testing, and in forensic cases. As the variations of benzodiazepines concentrations in biological samples during bleeding, postmortem changes, and redistribution could be biasing forensic medicine examinations, hence selecting a suitable sample and a validated accurate method is essential for the quantitative analysis of these main drug categories. The aim of this study was to develop a valid method for the determination of four benzodiazepines (flurazepam, lorazepam, alprazolam, and diazepam) in vitreous humor using liquid–liquid extraction and high-performance liquid chromatography. Methods: Sample preparation was carried out using liquid–liquid extraction with n-hexane: ethyl acetate and subsequent detection by high-performance liquid chromatography method coupled to diode array detector. This method was applied to quantify benzodiazepines in 21 authentic vitreous humor samples. Linear curve for each drug was obtained within the range of 30–3000 ng/mL with coefficient of correlation higher than 0.99. Results: The limit of detection and quantitation were 30 and 100 ng/mL respectively for four drugs. The method showed an appropriate intra- and inter-day precision (coefficient of variation forensic toxicology laboratory. PMID:27635251

  12. Studies on the post-ictal rise in seizure threshold. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Nutt, D.J.; Cowen, P.J.; Green, A.R.

    1981-05-08

    Seizure thresholds were determined by timed infusion of a convulsant drug. Following an electroconvulsive shock (ECS) rats exhibited a raised seizure threshold to infusion of the GABA antagonist drugs, pentylenetetrazol, bicuculline and isopropyl-bicyclophosphate, but not to the glycine antagonist strychnine or the 5-HT agonist, quipazine. The increase in threshold was seen following a bicuculline-induced seizure and 30 min following the last of a course of ECS given once daily for 10 days. The rise in seizure threshold still occurred when animals were pretreated with alpha-methyl-p-tyrosine (200 mg . kg-1), p-chlorophenylalanine (200 mg . kg-2), naloxone (1 mg . kg-1) or indomethacin (20 mg . kg-1). Diazepam (2 mg . kg-1), flurazepam (10 mg . kg-1) and sodium valproate (400 mg . kg-1) elevated basal seizure threshold and a further rise followed the ECS. Phenytoin (40 mg . kg-1) and carbamazepine (40 mg . kg-1) had no effect on basal seizure threshold or the ECS-induce rise. (

  13. Emerging role of orexin antagonists in insomnia therapeutics: An update on SORAs and DORAs.

    Science.gov (United States)

    Kumar, Anil; Chanana, Priyanka; Choudhary, Supriti

    2016-04-01

    The pharmacological management of insomnia has lately become a challenge for researchers worldwide. As per the third International Classification of Sleep disorders (ICSD-3) insomnia can be defined as a state with repeated difficulty in sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment. The conventional treatments approved for management of insomnia were benzodiazepines (BZDs) (estazolam, quazepam, triazolam, flurazepam and temazepam) and non-BZDs, also known as z-drugs (zaleplon, zolpidem, and eszopiclone), tricyclic antidepressant (TCA) doxepin as well as melatonin agonists, e.g. ramelteon. But the potential of these agents to address sleep problems has been limited due to substantial side effects associated with them like hangover, dependence and tolerance, rebound insomnia, muscular atonia, inhibition of respiratory system, cognitive dysfunctions, and increased anxiety. Recently, orexin neuropeptides have been identified as regulators of transition between wakefulness and sleep and documented to aid an initial transitory effect towards wakefulness by activating cholinergic/monoaminergic neural pathways of the ascending arousal system. This has led to the development of orexin peptides and receptors, as possible therapeutic targets for the treatment of sleep disorders with the advantage of having lesser side effects as compared to conventional treatments. The present review focuses on the orexin peptides and receptors signifying their physiological profile as well as the development of orexin receptor antagonists as novel strategies in sleep medicine. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Stability of 26 Sedative Hypnotics in Six Toxicological Matrices at Different Storage Conditions.

    Science.gov (United States)

    Mata, Dani C

    2016-10-01

    Forensic laboratories are challenged with backlogs that produce turnaround times that vary from days to months. Therefore, drug stability is important for interpretation in both antemortem (blood and urine) and postmortem (blood, brain, liver, stomach contents) cases. In this study, 23 benzodiazepines (2-hydroxyethylflurazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, α-hydroxyalprazolam, α-hydroxytriazolam, alprazolam, bromazepam, chlordiazepoxide, clonazepam, demoxepam, desalkylflurazepam, diazepam, estazolam, flunitrazepam, flurazepam, lorazepam, midazolam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam and triazolam) and three sedative hypnotics (zaleplon, zopiclone and zolpidem) were spiked into the six matrices at two different concentrations for each drug. The samples were stored in either a refrigerator (4°C) or freezer (-20°C) and analyzed in triplicate at various time intervals over an 8-month period using an SWGTOX validated method. The concentrations decreased over time regardless of the initial spiked concentration, and the storage conditions had little effect on the decrease of most drugs. Conversion from drug to metabolite was difficult to determine since all 26 drugs were present in each sample. Zopiclone and phenazepam were the least stable drugs; zopiclone was the only drug that completely disappeared in any matrix (both antemortem and postmortem blood). Urine was the most stable matrix with only phenazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, 2-hydroxyethylflurazepam, and zopiclone decreasing >20% over the 8 months in either storage condition. Postmortem blood, the least stable matrix, had only two drugs, zolpidem and bromazepam, decreasing <20% in the 8-month time period. Further experiments on stability of these drugs should be undertaken to remove the freeze-thaw cycle effect and more thoroughly examining drug-metabolite conversion. © The Author 2016. Published by Oxford University Press. All rights reserved. For

  15. Comparison of UHPLC and HPLC in benzodiazepines analysis of postmortem samples: a case-control study.

    Science.gov (United States)

    Behnoush, Behnam; Sheikhazadi, Ardeshir; Bazmi, Elham; Fattahi, Akbar; Sheikhazadi, Elham; Saberi Anary, Seyed Hossein

    2015-04-01

    The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC). In a case-control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods. Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples. In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis.

  16. Comparison of UHPLC and HPLC in Benzodiazepines Analysis of Postmortem Samples

    Science.gov (United States)

    Behnoush, Behnam; Sheikhazadi, Ardeshir; Bazmi, Elham; Fattahi, Akbar; Sheikhazadi, Elham; Saberi Anary, Seyed Hossein

    2015-01-01

    Abstract The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC). In a case–control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods. Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples. In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis. PMID:25860209

  17. A double-blind, placebo-controlled trial of dextromethorphan combined with clonidine in the treatment of heroin withdrawal.

    Science.gov (United States)

    Lin, Shih-Ku; Pan, Chun-Hung; Chen, Chia-Hui

    2014-08-01

    Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

  18. Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.

    Science.gov (United States)

    Blednov, Y A; Benavidez, J M; Black, M; Chandra, D; Homanics, G E; Rudolph, U; Harris, R A

    2013-04-01

    GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on α2-containing GABA(A)-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 (-/-) and α3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. LINKING GABAA RECEPTOR SUBUNITS TO ALCOHOL-INDUCED CONDITIONED TASTE AVERSION AND RECOVERY FROM ACUTE ALCOHOL INTOXICATION

    Science.gov (United States)

    Blednov, Y.A.; Benavidez, J.M.; Black, M.; Chandra, D.; Homanics, G.E.; Rudolph, U.; Harris, R.A.

    2012-01-01

    GABA type A receptors (GABAA-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABAA-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011) and indicate this aversive property of ethanol is dependent on ethanol action on α2-containing GABAA-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor-incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABAA-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 and α3 (-/-) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. PMID:23147414

  20. Determination of benzodiazepines in beverages using green extraction methods and capillary HPLC-UV detection.

    Science.gov (United States)

    Piergiovanni, Maurizio; Cappiello, Achille; Famiglini, Giorgio; Termopoli, Veronica; Palma, Pierangela

    2018-05-30

    Dispersive liquid-liquid microextraction with and without ultrasound assistance (DLLME, UA-DLLME) and microextraction with packed sorbent (MEPS) methods for the extraction and determination of eight different benzodiazepines (BDZ) (chlordiazepoxide, flurazepam, bromazepam, oxazepam, lorazepam, clobazam, clonazepam, and flunitrazepam) in three commercial non-alcoholic and light alcoholic beverages were optimized and compared. Benzodiazepines are frequently used for their extensive diffusion and strong numbing effect in drug-facilitated crimes (DFC). The tiny small amount of sample required for DLLME and MEPS extraction makes them very suitable for specimens collected at the crime scene of DFCs. Microextraction techniques are of increasing interest thanks to their accordance to green analytical chemistry (GAC) guidelines providing good recovery values. Ultrasound assistance (UA-DLLME) was used to investigate whether this type of energy can improve the recoveries of the analytes. Analyses of the extracts were performed with reverse-phase capillary high-performance liquid chromatography with UV detection (HPLC - UV), thanks to low environmental impact, robustness, diffusion, and affordability. Recovery percentages at three different concentrations in the three beverages were between 14.30% and 103.28% with intraday and interday RSD lower than ±2.78%. The same samples were extracted using a MEPS protocol, and the results were compared with those obtained with DLLME. MEPS gave recoveries between 20.90% and 101.88% for all matrices showing a better performance than DLLME at higher concentrations, though lower recoveries were observed with diluted samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. 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.

  2. Rapid determination of benzodiazepines, zolpidem and their metabolites in urine using direct injection liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Jeong, Yu-Dong; Kim, Min Kyung; Suh, Sung Ill; In, Moon Kyo; Kim, Jin Young; Paeng, Ki-Jung

    2015-12-01

    Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 μL) mixed with 80 μL of the IS solution were centrifuged. An aliquot (5 μL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm × 2.1 mm i.d., 3.5 μm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, α-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and α-hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0-104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully

  3. Therapy of unspecific tinnitus without organic cause.

    Science.gov (United States)

    Frank, Wilhelm; Konta, Brigitte; Seiler, Gerda

    2006-08-30

    (TRT) Unfortunately, the published results of the TRT are methodically frequently bad and scientific of a poor value. Many of the studies presented until now regarding tinnitus retraining therapy are not informative in their scientific context. In a study with 95 patients with a chronic tinnitus TRT could show a significant, more than six months lasting stable success by comparison to a combination of TET with group behaviour therapy (improvement be achieved around at least ten points in the tinnitus questionnaire (TF)). AD 5: PHARMACOLOGICAL THERAPIES Rheological drugs (medicines for hemodilution) could not show any statistically significant effect in the treatment of tinnitus. Studies to the medical treatment with tocainides (lidocaine) showed repeatable positive effects on tinnitus in higher dosages (as of 1.2 mg/day). Lamotrigine as a medicine had an effect positively only at with a small fraction of patients. Two studies with GABA receptor agonists could not prove therapeutic effects for tinnitus. Undesired side-effects were observed. Injections with Carvoverine (a glutamate antagonist) achieved significantly successes with a special form of tinnitus, the "Cochlear-synaptic tinnitus (CST)". A tricyclic antidepressant (Amitriptilin) could prove superiority against placebo. This effect could be confirmed in another study. However Clonazepame (a benzodiazepine), could not achieve any improvement. Short-term improvements were achieved with other benzodiazepines (Clonazepame, Diazepam, Flurazepame, Oxacepame and Alprazolame). A German retrospective study suggests a graded pharmacological therapy by means of rheological infusion therapy, applications of neurotransmitters, and injections of lidocaine. This method achieved a disappearance or a recovery of the complaints at 95.3% of the acute and 26.7% of the chronic cases. AD 6: SURGICAL PROCEDURES The effects of the operative excision of the stapes (stapedectomy) showed significant effects concerning tinnitus. This

  4. Therapy of unspecific tinnitus without organic cause

    Directory of Open Access Journals (Sweden)

    Seiler, Gerda

    2006-08-01

    training and structured group psychotherapy. Ad 4: Tinnitus Retraining Therapy (TRT: Unfortunately, the published results of the TRT are methodically frequently bad and scientific of a poor value. Many of the studies presented until now regarding tinnitus retraining therapy are not informative in their scientific context. In a study with 95 patients with a chronic tinnitus TRT could show a significant, more than six months lasting stable success by comparison to a combination of TET with group behaviour therapy (improvement be achieved around at least ten points in the tinnitus questionnaire (TF. Ad 5: Pharmacological therapies: Rheological drugs (medicines for hemodilution could not show any statistically significant effect in the treatment of tinnitus. Studies to the medical treatment with tocainides (lidocaine showed repeatable positive effects on tinnitus in higher dosages (as of 1.2 mg/day. Lamotrigine as a medicine had an effect positively only at with a small fraction of patients. Two studies with GABA receptor agonists could not prove therapeutic effects for tinnitus. Undesired side-effects were observed. Injections with Carvoverine (a glutamate antagonist achieved significantly successes with a special form of tinnitus, the “Cochlear-synaptic tinnitus (CST". A tricyclic antidepressant (Amitriptilin could prove superiority against placebo. This effect could be confirmed in another study. However Clonazepame (a benzodiazepine, could not achieve any improvement. Short-term improvements were achieved with other benzodiazepines (Clonazepame, Diazepam, Flurazepame, Oxacepame and Alprazolame. A German retrospective study suggests a graded pharmacological therapy by means of rheological infusion therapy, applications of neurotransmitters, and injections of lidocaine. This method achieved a disappearance or a recovery of the complaints at 95.3% of the acute and 26.7% of the chronic cases. Ad 6: Surgical procedures: The effects of the operative excision of the stapes