WorldWideScience

Sample records for prokinetic antiemetic anxiolytic

  1. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics.

    Science.gov (United States)

    Tonini, M; Cipollina, L; Poluzzi, E; Crema, F; Corazza, G R; De Ponti, F

    2004-02-15

    Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the

  2. Antiemetic research: future directions

    DEFF Research Database (Denmark)

    Olver, Ian; Molassiotis, Alexander; Aapro, Matti

    2011-01-01

    across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment...

  3. Enhanced Patient Expectant and Antiemetic Drug Efficacy

    Science.gov (United States)

    1999-07-01

    Breast Cancer Nausea and Vomiting Expectancy Patient Information Antiemetic Side Effect 15. NUMBER OF PAGES 15 16. PRICE CODE 17. SECURITY ...CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE Unclassified 19. SECURITY CLASSIFICATION OF ABSTRACT...5-HT3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy-related vomiting, this has

  4. Enhanced Patient Expectation and Antiemetic Drug Efficacy

    Science.gov (United States)

    1999-07-01

    NUMBER OF PAGES 15 Breast Cancer Expectancy Antiemetic Nausea and Vomiting Patient Information Side Effect 16. PRICE CODE 17. SECURITY CLASSIFICATION 18... SECURITY CLASSIFICATION OF THIS 19. SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF REPORT PAGE OF ABSTRACT Unclassified Unclassified...by the introduction of the 5-HT 3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy

  5. Anti-emetic principles of Poria cocos.

    Science.gov (United States)

    Tai, T; Akita, Y; Kinoshita, K; Koyama, K; Takahashi, K; Watanabe, K

    1995-12-01

    The triterpenes isolated from P. cocos and their derivatives were examined for anti-emetic activity. Some of these triterpenes inhibited emetic action induced by oral administration of copper sulfate pentahydrate to leopard frog. The triterpenes having an exomethylene group at C-24 showed anti-emetic activity to frogs.

  6. Essential oils and anxiolytic aromatherapy.

    Science.gov (United States)

    Setzer, William N

    2009-09-01

    A number of essential oils are currently in use as aromatherapy agents to relieve anxiety, stress, and depression. Popular anxiolytic oils include lavender (Lavandula angustifolia), rose (Rosa damascena), orange (Citrus sinensis), bergamot (Citrus aurantium), lemon (Citrus limon), sandalwood (Santalum album), clary sage (Salvia sclarea), Roman chamomile (Anthemis nobilis), and rose-scented geranium (Pelargonium spp.). This review discusses the chemical constituents and CNS effects of these aromatherapeutic essential oils, as well as recent studies on additional essential oils with anxiolytic activities.

  7. Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.

    Science.gov (United States)

    Mt-Isa, Shahrul; Tomlin, Stephen; Sutcliffe, Alastair; Underwood, Martin; Williamson, Paula; Croft, Nicholas M; Ashby, Deborah

    2015-04-01

    Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children. We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies. The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified. These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.

  8. Efficacy of prokinetic agents in improving bowel preparation for colonoscopy.

    Science.gov (United States)

    Mishima, Yuko; Amano, Yuji; Okita, Koichi; Takahashi, Yoshiko; Moriyama, Nobuyuki; Ishimura, Norihisa; Furuta, Kenji; Ishihara, Shunji; Adachi, Kyoichi; Kinoshita, Yoshikazu

    2008-01-01

    Colonoscopy plays an important role in the diagnosis and treatment of gastrointestinal illness in both Western countries and Japan. However, preparative bowel cleansing for colonoscopy is frequently troublesome for elderly and/or constipated patients, since they must drink larger volumes of lavage solution for adequate cleansing. We investigated the use of prokinetic agents for improving the efficacy and tolerability of bowel cleansing prior to colonoscopy. 613 patients were divided into two groups according to oral lavage solution used (polyethylene glycol or magnesium citrate), and were further randomized to receive either vehicle (100 ml water) alone, vehicle with 5 mg mosapride citrate, or vehicle with 50 mg itopride hydrochloride 30 min before administration of lavage solution. Experimental parameters included bowel cleansing quality, times to first defecation and completion of bowel cleansing, and incidence of uncomfortable abdominal symptoms during colonoscopy preparation. Administration of mosapride citrate or itopride hydrochloride prior to oral lavage solution did not significantly improve bowel cleansing quality. However, statistically significantly fewer uncomfortable abdominal symptoms were found in patients who received mosapride citrate or itopride hydrochloride versus vehicle alone. Prokinetic agents effectively decreased the incidence of uncomfortable abdominal symptoms experienced during colonoscopy preparation. Copyright 2008 S. Karger AG, Basel.

  9. Effect of clebopride, antidopaminergic gastrointestinal prokinetics, on cardiac repolarization.

    Science.gov (United States)

    Kim, Ki-Suk; Shin, Won-Ho; Park, Sang-joon; Kim, Eun-Joo

    2007-01-01

    The inhibition of the potassium current I(Kr) and QT prolongation has been known to be associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. In this study, the authors investigated the cardiac electrophysiological effects of clebopride, a class of antidopaminergic gastrointestinal prokinetic, that has been reported to prolong the QT interval by using the conventional microelectrode recording techniques in isolated rabbit Purkinje fiber and whole-cell patch clamp techniques in human ether-à-go-go-related gene (hERG)-stably transfected Chinese hamster ovarian (CHO) cells. Clebopride at 10 microM significantly decreased the Vmax of phase 0 depolarization (p Clebopride was found to have no effect on sodium channel currents. When these results were compared with Cmax (1.02 nM) of clinical dosage (1 mg, [p.o.]), it can be suggested that clebopride is safe at the clinical dosage of 1 mg from the electrophysiological aspect. These findings indicate that clebopride, an antidopaminergic gastrointestinal prokinetic drug, may provide a sufficient "safety factor" in terms of the electrophysiological threshold concentration. But, in a supratherapeutic concentration that might possibly be encountered during overdose or impaired metabolism, clebopride may have torsadogenic potency.

  10. Ondansetron. Therapeutic use as an antiemetic

    Energy Technology Data Exchange (ETDEWEB)

    Milne, R.J.; Heel, R.C. (Adis Drug Information Services, Auckland (New Zealand))

    1991-04-01

    Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs.

  11. Ondansetron. Therapeutic use as an antiemetic

    International Nuclear Information System (INIS)

    Milne, R.J.; Heel, R.C.

    1991-01-01

    Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs

  12. Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study.

    Science.gov (United States)

    Butt, Aroosa Ishtiaq; Khan, Bushra Tayyaba; Khan, Asma; Khan, Qamar-Uz-Zaman

    2017-01-01

    Gastroparesis and GERD occur concomitantly in 40 percent of the cases. Prokinetic drugs and acid blockers are employed as the main treatment modality. Ranitidine is an acid blocker with additional prokinetic activity and Itopride is a known prokinetic drug. This study was designed to observe the synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated duodenum of rabbits. Ranitidine (10-5-10-3) and itopride (10-6-10-5) were added in increasing concentrations to isolated duodenum of rabbits and contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative dose response curves were constructed. The potentiating prokinetic effect of Ranitidine on itopride was seen by using a fixed dose of ranitidine and cumulatively enhancing doses of itopride on iWorx. Ranitidine and itopride produced a dose dependent reversible contraction of the isolated tissue of rabbits with ranitidine showing a max response of 0.124mV and itopride showing a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic effect of itopride at low doses but at high dose the effect began to wane off. Ranitidine and itopride produce a statistically significant synergistic potentiating prokinetic effect at low doses in vitro.

  13. 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.

  14. Antiemetic prophylaxis with promethazine or ondansetron in major

    African Journals Online (AJOL)

    Studio G5

    of PONV.2–8 Traditional antiemetic drugs (e.g. promethazine, metoclopramide ... a developing country's health care delivery system because of ..... Comparison of the bioavailability of oral, rectal and intramuscular promethazine. Biopharm ...

  15. [Research on antiemetics: an Italian model of success].

    Science.gov (United States)

    Roila, F

    1998-01-01

    At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for

  16. Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia.

    Science.gov (United States)

    Hiyama, Toru; Yoshihara, Masaharu; Matsuo, Keitaro; Kusunoki, Hiroaki; Kamada, Tomoari; Ito, Masanori; Tanaka, Shinji; Nishi, Nobuo; Chayama, Kazuaki; Haruma, Ken

    2007-03-01

    Functional dyspepsia (FD) is often treated with prokinetic agents; however, the efficacy of prokinetic agents in patients with FD has been questioned recently. The aim of this study was to perform a meta-analysis of the effects of prokinetic agents in patients with FD. Prokinetic agents, including metoclopramide, domperidone, trimebutine, cisapride, itopride and mosapride, used for treatment of FD between 1951 and 2005 were identified. Twenty-seven studies were selected. Difference in the probability of response between the interventional drug and placebo was used as a summary statistic for the treatment effect. Meta-regression analysis was used to detect sources of heterogeneity. In total, 1844 subjects were assigned to an experimental arm, and 1591 subjects were assigned to a placebo arm. Publication bias was ruled out by funnel plot and statistical testing (P = 0.975). In the overall analysis, the summary statistic was 0.295 (95% confidence interval: 0.208-0.382, P < 0.001), indicating that the interventional drug has 30% excess probability of producing a response compared with placebo. The most significant source of heterogeneity was the year of publication (P < 0.001). The data clearly indicate that prokinetic agents are significantly more effective than placebo in the treatment of FD. Although FD is a chronic condition, efficacy was assessed over short periods. Long-term randomized controlled trials are needed to confirm the effect.

  17. Pseudopheochromocytoma induced by anxiolytic withdrawal.

    Science.gov (United States)

    Páll, Alida; Becs, Gergely; Erdei, Annamária; Sira, Lívia; Czifra, Arpád; Barna, Sándor; Kovács, Péter; Páll, Dénes; Pfliegler, György; Paragh, György; Szabó, Zoltán

    2014-10-08

    Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.

  18. Electrogastrography associated with symptomatic changes after prokinetic drug treatment for functional dyspepsia.

    Science.gov (United States)

    Lim, Hyun Chul; Lee, Sang In; Chen, Jiande D Z; Park, Hyojin

    2012-11-07

    To evaluate the effect of prokinetic drugs on electrogastrography (EGG) parameters according to symptomatic changes in patients with functional dyspepsia (FD). Seventy-four patients with FD were prospectively enrolled in this study between December 2006 and December 2010. We surveyed the patients using a questionnaire on dyspeptic symptoms before and after an 8-wk course of prokinetic drug treatment. We also measured cutaneous pre-prandial and post-prandial EGG recordings including percentage of gastric waves (normogastria, bradygastria, tachygastria), dominant frequency (DF), dominant power (DP), dominant frequency instability coefficient (DFIC), dominant power instability coefficient (DPIC), and the ratio of post-prandial to fasting in DP before and after the 8-wk course of prokinetic drug treatment. Fifty-two patients (70%) achieved symptomatic improvement after prokinetic drug treatment. Patients who had normal gastric slow waves showed symptom improvement group after treatment. Post-prandial DF showed a downward trend in the symptom improvement group, especially in the itopride group. Post-prandial DP was increased regardless of symptom improvement, especially in the itopride group and mosapride group. Post-prandial DFIC and DPIC in the symptom improvement group were significantly increased after the treatment. The EGG power ratio was increased after treatment in the symptom improvement group (0.50 ± 0.70 vs 0.93 ± 1.77, P = 0.002), especially in the itopride and levosulpiride groups. Prokinetics could improve the symptoms of FD by regulating gastric myoelectrical activity, and EGG could be a useful tool in evaluating the effects of various prokinetics.

  19. [MODERN PROKINETICS AND THEIR ROLE IN THE TREATMENT OF GASTROENTEROLOGICAL PATHOLOGY].

    Science.gov (United States)

    Sheptulin, A A; Belousova, I B

    2016-01-01

    The importance of prokinetics (drugs stimulating motor function of the gastrointestinal tract) arises from the high prevalence of gastroenterological pathology associated with primary or secondary disturbances of this function in esophagus, stomach, and intestines. The main groups of prokinetics are beta-blockers of dopamine receptors, inhibitors of acetylcholine esterase (or their combination with dopamine receptor blockers), 5-HT4-receptor agonists. They find wide application for the treatment of gastroesophgeal reflux disease, functional dyspepsia and constipation, obstipational form of irritable bowel syndrome, and other conditions accompanied by motor function disorders of the gastrointestinal tract.

  20. Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats

    NARCIS (Netherlands)

    de Winter, B. Y.; Boeckxstaens, G. E.; de Man, J. G.; Moreels, T. G.; Schuurkes, J. A.; Peeters, T. L.; Herman, A. G.; Pelckmans, P. A.

    1999-01-01

    BACKGROUND/AIM: The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT(3)) receptor

  1. [Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].

    Science.gov (United States)

    Li, Fujun; Zou, Yiyou; Huang, Tianhui

    2009-07-01

    To determine the effect of prokinetic agents such as domperidone, mosapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats,and also to explore the mechanism. The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the interdigestive phase. The effect of the prokinetic agents on the amplitude and frequency of gastric and duodenal electromyogram in the SD rats was compared. The antagonists such as atropine, phentolamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats(Pitopride was the most obvious among the 3 groups (Pitopride, and physiological saline were inhibited by atropine(PItopride, mosapride, domperidone, and clarithromycin can increase the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

  2. Therapeutic Response for Functional Abdominal Pain in Children with Occult Constipation: Laxatives versus Prokinetic Drugs.

    Science.gov (United States)

    Ha, Eun Kyo; Jang, Homin; Jeong, Su Jin

    2017-01-01

    The relationship between functional abdominal pain (FAP) and occult constipation (OC) in children who did not meet the Rome III criteria for constipation has rarely been reported. This study aimed to estimate the prevalence of OC in patients with FAP and to compare the effectiveness of prokinetic drugs and laxatives for FAP and OC. Pediatric outpatients (n = 212; aged 4-15 years) who satisfied the Rome III criteria for childhood FAP were divided into 2 groups based on Leech scores: group 1 pain severity was assessed after 2 weeks, 1 month, and 3 months. A total 52.4% (111/212) of patients had OC in this study. More patients who received laxatives had reduced pain scores compared with those who received prokinetic drugs. Those treated with laxatives in group 2 had a better response than those treated with prokinetic drugs throughout the study period (P < 0.001, P < 0.001, and P = 0.002 after 2 weeks, 1 month, and 3 months, respectively). OC was frequently encountered in children with FAP. Laxatives can be more effective than prokinetic drugs for relieving symptoms of FAP in children with a Leech score ≥ 8 and suspected OC.

  3. Role of prophylactic antiemetics in oral and maxillofacial surgery

    International Nuclear Information System (INIS)

    Hanif, S.; Warraich, R.A.; Khan, S.R.; Riaz, N.; Mehdi, A.J.

    2014-01-01

    To find out the occurrence of postoperative nausea and vomiting (PONY) in oral and maxillofacial surgery done under general anaesthesia and to evaluate the purpose of using prophylactic antiemetic drugs. Design: Observational study. Place and Duration of the Study: Oral and Maxillofacial Department, KEMU / Mayo Hospital Lahore, from September 20 II to June 2012. Method: The number of patients who were operated in oral and maxillofacial surgery ward irrespective of age and gender for this study were 240. Risk factors related with PONY including gender, anesthetic drug used, surgical procedure, approach' used, total time of surgery and postoperative use of opioids were investigated. A wait and watch scheme was followed in patients with complaint of PONY. Antiemetics to be given in those cases where more than 2 episodes of vomiting took place. Results: It was found out that only II patients experienced from nausea and vomiting in post operative period. A notable relation was seen between PONY and female population, total time of surgery, anesthetic drug, surgery of tumor and temporomandibular joint. The surgical approach and opioids in postoperative period for PONY were found to be insignificant. Conclusion: PONY is not a significant finding in oral and maxillofacial surgery. We find out that there is no logic for the use of prophylactic antiemetic drugs in maxillofacial surgery. (author)

  4. Evaluation of new gastro-intestinal prokinetic (ENGIP-II) study.

    Science.gov (United States)

    Walwaikar, Pradeep P; Kulkarni, Sujay S; Bargaje, Rahul S

    2005-12-01

    Non-ulcer dyspepsia is a common clinical disorder characterised by reduced gastric motility. Safety concerns have restricted use of currently available prokinetic drugs. Itopride is a new safer prokinetic drug with dopamine D2 antagonism and acetylcholinesterase inhibitory actions. The ENGIP-II study was conducted to investigate the efficacy, and safety of itopride in patients of non-ulcer dyspepsia. There were significant reductions in upper abdominal pain, heartburn frequency, gastro-oesophageal regurgitation, nausea, bloating, early satiety after meals at day 3 only; whereas significant improvements were noted in belching, anorexia at day 6 and in vomiting at day 9. Thus, ENGIP-II study shows that itopride was well tolerated patients and appears to be the drug of choice in patients with non-ulcer dyspepsia.

  5. A Prokinetic Agent with a Dual Effect – Itopride – In the Treatment of Dysmotility

    OpenAIRE

    Petr Dite; Martin Rydlo; Milan Dockal; Arnost Martinek

    2014-01-01

    A wide range of dyspeptic symptoms in clinical practice reflect the high prevalence of functional disorders of the gastrointestinal (GI) tract. Prokinetic agents are the current mainstay in the therapy of functional dyspepsia. One of these drugs is itopride. We evaluated therapeutic efficacy of itopride according to the literature review. The therapeutic potential of itopride is connected with a dual effect: influencing of enzyme acetylcholinesterase activity and blocking dopamine D2 receptor...

  6. Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis.

    Science.gov (United States)

    Yang, Young Joo; Bang, Chang Seok; Baik, Gwang Ho; Park, Tae Young; Shin, Suk Pyo; Suk, Ki Tae; Kim, Dong Joon

    2017-06-26

    Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27-6.06), mosapride (OR: 1.99, 95% credible interval: 0.87-4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92-4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29-6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43-6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07-1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04-2.18). Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD.

  7. Bioavailability of the antiemetic metopimazine given as a microenema

    DEFF Research Database (Denmark)

    Herrstedt, J.; Jørgensen, M.; Angelo, H.R.

    1996-01-01

    The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite ...... were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration....

  8. Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

    Science.gov (United States)

    Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

    2014-01-01

    AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

  9. 3H-labeling of prokinetic motilide ABT-229 for biodistribution and metabolism studies

    International Nuclear Information System (INIS)

    Faghih, Ramin; Burnell-Curty, Cynthia; Surber, Bruce; Shoghi, Simin; Borre, Anthony; Ye Yao; Lartey, P.A.; Nellans, H.N.

    1996-01-01

    The prokinetic drug candidate, ABT-229, has been successfully [ 3 H]-labeled in the macrolactone ring. This was accomplished with [ 3 H]-NaBH 4 reduction of the 11-ketone analog in a four step synthetic sequence beginning with the drug candidate. The 3 H-labeled drug was obtained with specific activity of 9.0 Ci/mmol and radiochemical purity > 99%. This constitutes the first methodology for 3 H-labeling of the macrolactone in an erythromycin derivative. (author)

  10. A Prokinetic Agent with a Dual Effect – Itopride – In the Treatment of Dysmotility

    Directory of Open Access Journals (Sweden)

    Petr Dite

    2014-12-01

    Full Text Available A wide range of dyspeptic symptoms in clinical practice reflect the high prevalence of functional disorders of the gastrointestinal (GI tract. Prokinetic agents are the current mainstay in the therapy of functional dyspepsia. One of these drugs is itopride. We evaluated therapeutic efficacy of itopride according to the literature review. The therapeutic potential of itopride is connected with a dual effect: influencing of enzyme acetylcholinesterase activity and blocking dopamine D2 receptors. After the itopride administration, the contractility of smooth muscle in the upper GI tract increases. Itopride is a drug with rapid absorption from the small bowel; its peak serum concentration occurs 35 minutes after oral administration. Itopride does not pass the blood-brain barrier and does not affect the heart rate by influencing the QT segment. Itopride is a safe prokinetic agent with positive influence on the symptoms of functional dyspepsia such as postprandial fullness, bloating, and gastric emptying. Itopride could also be used for the therapy of the mild form of gastro-oesophageal reflux.

  11. Support for Natural Small-Molecule Phenols as Anxiolytics

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2017-12-01

    Full Text Available Natural small-molecule phenols (NSMPs share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were assayed with the elevated plus maze (EPM test in mice. The oral doses were 5, 10 and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10 mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl group in 4-hydroxycinnamic acid (4-OH CA was essential for the anxiolytic activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl CA. The in vivo spike recording of rats’ hippocampal neurons also showed significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal spike recording results converged to indicate the hippocampal CA1 region might be a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides further experimental data supporting NSMPs sharing anxiolytic activity, which may have general implications for phytotherapy because small phenols occur extensively in herbal medicines.

  12. Systematic review: Antacids, H2-receptor antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia.

    Science.gov (United States)

    Moayyedi, P; Soo, S; Deeks, J; Forman, D; Harris, A; Innes, M; Delaney, B

    2003-05-15

    Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting. To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia. Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse. Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias. The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues.

  13. Optimizing antiemetic therapy in multiple-day and multiple cycles of chemotherapy

    DEFF Research Database (Denmark)

    Ellebaek, E.; Herrstedt, J.

    2008-01-01

    PURPOSE OF REVIEW: Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining...... of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated...... that the dopamine D2-receptor antagonist metopimazine has some additive effect on delayed symptoms induced by multiple-day chemotherapy. SUMMARY: The development of the NK1-receptor antagonist aprepitant has significantly improved the antiemetic control in patients treated with multiple cycles of chemotherapy. Far...

  14. Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome.

    Science.gov (United States)

    Kawai, T; Kinoshita, K; Koyama, K; Takahashi, K

    1994-02-01

    Magnolol and honokiol, biphenyl compounds, were isolated as anti-emetic principles from the methanolic extract of Magnolia obovata bark. [6]-, [8]-, and [10]-shogaols and [6]-, [8]-, and [10]-gingerols were isolated from the methanolic extract of Zingiber officinale rhizome as anti-emetic principles. Some phenyl-propanoids with allyl side-chains were found to show the same activity. They inhibited the emetic action induced by the oral administration of copper sulfate pentahydrate to leopard and ranid frogs.

  15. Effectiveness of antiemetics in control of antineoplastic chemotherapy-induced emesis at home

    OpenAIRE

    Castro,Marielly Cunha; Araújo,Suely Amorim de; Mendes,Thaís Rezende; Vilarinho,Glauciane Silva; Mendonça,Maria Angélica Oliveira

    2014-01-01

    Objective Evaluating if antiemetics are effective in the prevention or treatment at home, of chemotherapy-induced emesis. Methods In total, were included 42 women with breast cancer in moderately emetogenic chemotherapy, using dexamethasone/ondansetron before each cycle. The frequency of nausea and vomiting was obtained by applying the instrument in the pre-chemotherapy period, and 24h, 48h, 72h and 96h after chemotherapy. The use of antiemetics was considered in accordance with adherence...

  16. Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora

    Directory of Open Access Journals (Sweden)

    Najeeb-ur-Rehman

    2012-03-01

    Full Text Available Abstract Background Fumaria parviflora Linn. (Fumariaceae, is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of Fumaria parviflora in gut motility disorders. Methods The in-vivo prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum from different animal species (mouse, guinea-pig and rabbit were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system. Results The aqueous-methanol extract of Fumaria parviflora (Fp.Cr, which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the in-vivo in mice at 30 and 100 mg/kg. In the in-vitro studies, Fp.Cr (0.01-1 mg/ml caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum, and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum, the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive. This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse. Conclusions This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of Fumaria parviflora in gut motility disorders such as, indigestion and constipation. This study also suggests using

  17. Aerial parts of maca (Lepidium meyenii Walp.) as functional vegetables with gastrointestinal prokinetic efficacy in vivo.

    Science.gov (United States)

    Jin, Wenwen; Chen, Xuemin; Huo, Qing; Cui, Yajie; Yu, Zejun; Yu, Longjiang

    2018-06-20

    Lepidium meyenii Walp. (maca) has been utilized in the Andean region because of its edibleness and medicinal value. The aerial parts of maca (APM) were analyzed for protein, total sugar, vitamins, amino acids, and minerals and its characteristic active ingredients at five different growth stages. The results showed the high protein, total sugar, vitamin C, niacin, potassium, and calcium contents of APM. All 17 amino acids and the characteristic active ingredients, namely, macamide, glucosinolates, adenosine, and total saponins, were detected. We examined the effects of maca plant powders on gastric emptying and intestinal propulsion and the levels of serum motilin and gastrin in atropine-treated mice. Benzyl isothiocyanate (BITC) was investigated to identify the potential active material in APM. The results revealed that both maca plant powders and BITC can promote the gastrointestinal prokinetic efficacy. Thus, APM feature potential as new functional vegetable sources.

  18. Anti-emetic principles of Inula linariaefolia flowers and Forsythia suspensa fruits.

    Science.gov (United States)

    Kinoshita, K; Kawai, T; Imaizumi, T; Akita, Y; Koyama, K; Takahashi, K

    1996-05-01

    The anti-emetic effects of 40 extracts made from 12 traditional Chinese herbal drugs were examined. Ten extracts inhibited emesis induced by copper sulfate pentahydrate; all were administered orally, and one extract inhibited emesis induced by apomorphine hydrochloride given to leopard and ranid frogs. Taraxasteryl palmitate and acetate, bigelovin and dihydrobigelovin were isolated from the CHCl(3) extract of Inula linariaefolia flowers, and identified as the active antiemetic agents when emesis was induced by copper sulfate. In addition, chlorogenic acid was isolated from the MeOH extract as an anti-emetic principle for the emesis induced by apomorphine hydrochloride. Rengyol, phillyrin and rutin were isolated from the MeOH extract of Forsythia suspensa fruits and identified as the inhibitors of emesis induced by copper sulfate pentahydrate. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  19. Comparison of Antiemetic Effects of Ondansetron, Granisetron and Tropisetron in Treatment of Acute Emesis Caused By Cisplatin/Paclitaxel Chemotherapy

    Directory of Open Access Journals (Sweden)

    Taner Turan

    2016-06-01

    CONCLUSION: Although this study is not prospective, it is homogenous for treatment modalities and patient selection. Complete response was observed in 63% of courses; however this antiemetic affect is not found to be satisfactory. In order to develope better protocols there is need for prospective studies on homogenous group. Antiemetic efficiency has to associate for chemotherapy protocols.

  20. Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study.

    Science.gov (United States)

    Kim, Yong Sung; Kim, Tae Hyeon; Choi, Chang Soo; Shon, Young Woo; Kim, Sang Wook; Seo, Geom Seog; Nah, Yong Ho; Choi, Myung Gyu; Choi, Suck Chei

    2005-07-21

    Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pHitopride thrice a day (t.i.d.) for 30 d in random order, using an open label method. For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment. Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pHitopride in both groups. Itopride 100 mg t.i.d. is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.

  1. [Comparative data of prokinetics in treatment of gastroesophageal reflux disease in patients with diabetes].

    Science.gov (United States)

    Fedorchenko, Iu L

    2013-01-01

    The purpose is to evaluate the effectiveness of itopride (IP) and domperidone (DP) in the treatment of patients with gastroesophageal reflux disease (GERD), in combination with diabetes mellitus (DM) type 1 and 2. 40 patients were examined with GERD and type 1 diabetes and 50 patients with GERD and type 2 diabetes. Each group of patients with GERD, DM 1 and 2 has been divided into: the basic subgroup receiving IG 50 mg 3 tid and control--DP 10 mg tid. Patients were also administered omeprazole. Both subgroups were strictly randomized to key indicators, except for therapy. Baseline and after 2 and 4 weeks, all patients were examined to identify complaints, endoscopy and pH-metric changes, gastric motility was studied by electrogastroenterographic method (PEGEG). In the subgroups of patients with GERD + DM 1 and GERD + DM 2, received treatment with IG complaints on heartburn, regurgitation, odynophagia relieved significantly earlier then in the subgroups treated with DP. After 4 weeks of therapy, decreasing in the number of gastroesophageal refluxes, number of patients with erosive esophagitis B level, and normalization of the motility of the stomach were significantly higher in the groups of GERD + DM 1 and GERD + DM 2 received treatment with IG when compared with the subgroup of PD. There were no side effects of prokinetics. IG was more effective then DP in the treatment of GERD in patients with diabetes, and may be recommended for inclusion in the scheme of treatment of this comorbidity.

  2. [The use of prokinetics for the correction of motor and tonic digestive disorders].

    Science.gov (United States)

    Maev, I V; Samsonov, A A; Karmanova, E A; Ivanchenko, E A

    2009-01-01

    Abnormal tonic-motor activity is a key component in pathogenesis of many digestive disorders. Secondary disturbance of tonic-motor activity of digestive organs and the accompanying symptoms are known to develop in conjunction with diseases of other organs and systems, diabetes mellitus, Parkinson's disease, myotonic muscular dystrophy, amyloidosis, hyper- and hypothyroidism, hypoparathyroidism, etc. Disturbed motor activity in the gastro-duodenal region most frequently underlies functional dyspepsia, i.e. a group of symptoms unrelated to organic, systemic and metabolic diseases. Prokinetics are an important class of medicinal products for the treatment of all clinical forms of dyspepsia. One of the new ones is itopride hdrochloride having combined mechanism of action. Clinical studies of this drug revealed its high efficiency in patients with functional dyspepsia, chronic gastritis, and diabetic gastroparesis. It is well tolerated by the patients and produces no serious side effects. Inclusion of this drug in therapy improves the outcome of the treatment of disturbed motor activity of the gastrointestinal tract.

  3. Withaferin-A displays enhanced anxiolytic efficacy without tolerance ...

    African Journals Online (AJOL)

    Withaferin-A dose-dependently (10 tob40 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of withaferin-A at 40.0 mg/kg significantly (P<0.05) increased open arm ...

  4. Anxiolytic - like properties of Hallea ciliata in mice | Stephanie ...

    African Journals Online (AJOL)

    Background: The aim of the present study was to evaluate the anxiolytic properties of the decoction of stem bark of Hallea ciliate in mice. The decoction of Hallea ciliata is used in traditional medicine in Cameroon to treat diseases like anxiety disorders, fever, infantile convulsions and malaria. Materials and Methods: Stress ...

  5. Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

    Science.gov (United States)

    Inui, Naoki

    2017-05-01

    Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

  6. Efficacy of prokinetics with a split-dose of polyethylene glycol in bowel preparation for morning colonoscopy: a randomized controlled trial.

    Science.gov (United States)

    Kim, Hyoung Jun; Kim, Tae Oh; Shin, Bong Chul; Woo, Jae Gon; Seo, Eun Hee; Joo, Hee Rin; Heo, Nae-Yun; Park, Jongha; Park, Seung Ha; Yang, Sung Yeon; Moon, Young Soo; Shin, Jin-Yong; Lee, Nae Young

    2012-01-01

    Currently, a split-dose of polyethylene glycol (PEG) is the mainstay of bowel preparation due to its tolerability, bowel-cleansing action, and safety. However, bowel preparation with PEG is suboptimal because residual fluid reduces the polyp detection rate and requires a more thorough colon inspection. The aim of our study was to demonstrate the efficacy of a sufficient dose of prokinetics on bowel cleansing together with split-dose PEG. A prospective endoscopist-blinded study was conducted. Patients were randomly allocated to two groups: prokinetic with split-dose PEG or split-dose PEG alone. A prokinetic [100 mg itopride (Itomed)], was administered twice simultaneously with each split-dose of PEG. Bowel-cleansing efficacy was measured by endoscopists using the Ottawa scale and the segmental fluidity scale score. Each participant completed a bowel preparation survey. Mean scores from the Ottawa scale, segmental fluid scale, and rate of poor preparation were compared between both groups. Patients in the prokinetics with split-dose PEG group showed significantly lower total Ottawa and segmental fluid scores compared with patients in the split-dose of PEG alone group. A sufficient dose of prokinetics with a split-dose of PEG showed efficacy in bowel cleansing for morning colonoscopy, largely due to the reduction in colonic fluid. Copyright © 2012 S. Karger AG, Basel.

  7. Antiemetic therapy in Asia Pacific countries for patients receiving moderately and highly emetogenic chemotherapy--a descriptive analysis of practice patterns, antiemetic quality of care, and use of antiemetic guidelines.

    Science.gov (United States)

    Yu, Shiying; Burke, Thomas A; Chan, Alexandre; Kim, Hoon-Kyo; Hsieh, Ruey Kuen; Hu, Xichun; Liang, Jin-Tung; Baños, Ana; Spiteri, Carmel; Keefe, Dorothy M K

    2015-01-01

    This paper reports prescribing patterns for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). Evaluable patients in cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56 (12) years, including 58% women. For the acute phase after HEC, overall (and country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%) corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%), corticosteroid (37%), and/or NK1-RA (4%). The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase.

  8. Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy

    International Nuclear Information System (INIS)

    Yamasaki, Fumiyuki; Watanabe, Yosuke; Nosaka, Ryo

    2014-01-01

    Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. Between December 2011 and January 2013, 34 patients (19 males, 15 females; age range, 3-80 years) received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting (grade 1) or nausea (grade 2) were treated with granisetron as a rescue anti-emetic. Episodes were graded as no vomiting, no nausea, no anti-emetic; no vomiting, nausea, no anti-emetic; no vomiting, nausea with anti-emetic; and vomiting. Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5 (55.6%) experienced grade 2 nausea or vomiting. Two of 6 patients (33.3%) treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients (16.7%) who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia (p<0.05). Complete response (no vomiting, no additional rescue anti-emetic, and no nausea) was observed in 5 of 9 patients treated with granisetron. Four of 9 patients (44.4%) treated with granisetron experienced constipation (grade 1 or 2); its administration had no major adverse effects in our study population. Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation. (author)

  9. Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

    Science.gov (United States)

    de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

    1998-01-01

    We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

  10. Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.

    Science.gov (United States)

    Zanon, Davide; Gallelli, Luca; Rovere, Francesca; Paparazzo, Rossella; Maximova, Natalia; Lazzerini, Marzia; Reale, Antonio; Corsetti, Tiziana; Renna, Salvatore; Emanueli, Tullia; Mannelli, Francesco; Manteghetti, Francesco; Da Dalt, Liviana; Palleria, Caterina; Banchieri, Nicola; Urbino, Antonio; Miglietta, Mario; Cardoni, Giovanni; Pompilio, Adriana; Arrighini, Alberto; Lazzari, Clara; Messi, Gianni

    2013-03-01

    Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.

  11. Survey of Implementation of Antiemetic Prescription Standards in Indian Oncology Practices and Its Adherence to the American Society of Clinical Oncology Antiemetic Clinical Guideline

    Directory of Open Access Journals (Sweden)

    Vijay Patil

    2017-08-01

    Full Text Available Purpose: Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. Methods: This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. Results: Sixty-six (62.9% of 105 responded and 65 centers (98.5% were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8% than the highly emetogenic regimens (6.1%. The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%, lack of national guidelines (12 centers; 18.2%, and lack of administrative support (10 centers; 15.2%. Conclusion: Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.

  12. Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

    Science.gov (United States)

    Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

    2017-05-17

    The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

  13. Anxiolytic-like effect of Sonchus oleraceus L. in mice.

    Science.gov (United States)

    Cardoso Vilela, Fabiana; Soncini, Roseli; Giusti-Paiva, Alexandre

    2009-07-15

    Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system. This study was conducted to establish the anxiolytic effect of extracts from the aerial parts of Sonchus oleraceus. This study evaluated the effect of hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice submitted to the elevated plus-maze and open-field tests. Clonazepam was used as the standard drug. In the elevated plus-maze test, the Sonchus oleraceus extracts increased the percentage of open arm entries (PSonchus oleraceus extract exerts an anxiolytic-like effect on mice.

  14. Anxiolytic-like effects of erythrinian alkaloids from Erythrina suberosa

    Energy Technology Data Exchange (ETDEWEB)

    Serrano, Maria Amelia R.; Batista, Andrea N. de L.; Bolzani, Vanderlan da S.; Santos, Luciana de A. [UNESP, Araraquara, SP (Brazil). Inst. de Quimica; Nogueira, Paulo J. de C.; Nunes-de-Souza, Ricardo L. [UNESP, Araraquara, SP (Brazil). Faculdade de Ciencias Farmaceuticas; Latif, Abdul; Arfan, Mohammad [University of Peshawar, Peshawar (Pakistan). Inst. of Chemical Sciences

    2011-07-01

    Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM). (author)

  15. Anxiolytic-like effects of erythrinian alkaloids from Erythrina suberosa

    International Nuclear Information System (INIS)

    Serrano, Maria Amelia R.; Batista, Andrea N. de L.; Bolzani, Vanderlan da S.; Santos, Luciana de A.; Nogueira, Paulo J. de C.; Nunes-de-Souza, Ricardo L.; Latif, Abdul; Arfan, Mohammad

    2011-01-01

    Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM). (author)

  16. 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.

  17. Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.

    1983-01-01

    A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning

  18. The role of anxiolytic premedication in reducing preoperative anxiety.

    LENUS (Irish Health Repository)

    Carroll, Jennifer K

    2012-01-01

    Prevention of preoperative anxiety with anxiolytic premedication is associated with improved preoperative outcomes in surgical patients. The objective of the authors\\' study was to evaluate the percentage of surgical patients that are prescribed premedication for preoperative anxiety before their anticipated surgical procedure. A prospective study was carried out by theatre nursing staff in the theatre reception bay of a university teaching hospital. A questionnaire was designed to record the number of patients that described symptoms consistent with preoperative anxiety. The number of patients that had been offered anxiolytic premedication for preoperative anxiety was also recorded. Consent was obtained from 115 consecutive surgical patients (male, n=52; female, n=63). Of these, 66% (n=76) reported anxiety before their surgical procedure (male: n=27, female: n=49). Premedication with a low-dose benzodiazepine was prescribed by an anaesthetist in 4% of cases (n=5). Patients that received premedication preoperatively reported effective relief of their anxiety symptoms This study demonstrates that preoperative patient anxiety is highly prevalent. The authors\\' findings suggest that premedication with anxiolytic pharmacological therapy may be an underused therapeutic resource for managing preoperative patient anxiety.

  19. [The onset of physiological activity in the stomach in the postoperative period. A comparative study with a prokinetic preparation, Ganaton].

    Science.gov (United States)

    Frasko, R; Maruna, P; Gürlich, R

    2004-10-01

    Postoperative gastroparesis decreases patient's postoperative comfort. The aim of this prospective study was to assess efficacy of the peroperatively administered prokinetic preparation Ganaton (Itopridi hydrochloridum, Abbott) on the postoperative gastroparesis. This prospective study was conducted in the Ist Surgical Clinic of the 1st Medical Faculty in Prague in 2001-2001. The total of 64 patients took part in this study. The patients underwent either a non-adjustable bandaging of the stomach via laparoscopy for a severe obesity, or a laparoscopic cholecystectomy. In the postoperative period, a subjective status of each patient, as well as objective examinations (auscultaion, gas excretion, stool excretion) and a percutaneous electrographic record were recorded. The patients after both the gastric bandaging and the laparoscopic cholecystectomy, demonstrated faster restoration of the physiological stomach contractions frequency in the group with itopride, compared with the placebo group. The prokinetic preparation was well tolerated and the authors did not record any undesirable side-effects. The preparation significantly speeded up restoration of the physiological stomach contractions frequency compared with the placebo group. Based on our results, its administration is a suitable part of the prophylaxis and treatment of the postoperative gastroparesis.

  20. Evaluation of antiemetic activities of alcoholic extract of grewia asiatica in experimental model dog

    International Nuclear Information System (INIS)

    Yaqeen, Z.; Shail, T.; Rahman, A.U.; Saleem, M.

    2008-01-01

    The fruits of Grewia asiatica were evaluated for the antiemetic activity in the experimental model dogs, whereas, acute oral toxicity test was carried out in mice and rats. Maximum oral dose of 200 mg/kg and 600 mg/kg of crude alcoholic extract was found non toxic in mice and rats. Oral dose of crude alcoholic extract (120 mg/kg body weight) caused antiemetic effect in dogs in 3 h and controlled emesis centrally induced by Apomorphine (0.044 mg/kg body weight). This activity of G asiatica was comparable with standard commercial anti-emctic drugs like Maxolon (Metoclopramide) and Largactil tablets 10 mg (Chlorpromazine) of M/s. Aventis Pharma., Pakistan. (author)

  1. Development and evaluation of a sublingual film of the antiemetic granisetron hydrochloride.

    Science.gov (United States)

    Kalia, Vani; Garg, Tarun; Rath, Gautam; Goyal, Amit Kumar

    2016-05-01

    The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.

  2. Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy.

    Science.gov (United States)

    Uchida, M; Nakamura, T; Makihara, Y; Suetsugu, K; Ikesue, H; Mori, Y; Kato, K; Shiratsuchi, M; Hosohata, K; Miyamoto, T; Akashi, K

    2018-05-01

    The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.

  3. Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

    Science.gov (United States)

    Lauretti, G R; Mattos, A L; Gomes, J M; Pereira, N L

    1997-01-01

    Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.

  4. Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

    Science.gov (United States)

    Ho, Robin S T; Chung, Vincent C H; Wong, Charlene H L; Wu, Justin C Y; Wong, Samuel Y S; Wu, Irene X Y

    2017-09-04

    Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.

  5. Anxiolytic and nootropic activity of Vetiveria zizanioides roots in mice

    Directory of Open Access Journals (Sweden)

    Abhijit M Nirwane

    2015-01-01

    Full Text Available Background: Vetiveria zizanioides (VZ (family: Poaceae, an aromatic plant commonly known as “Vetiver“ has been used for various ailments. Concerning the various ailments being listed as the traditional uses of VZ, no mention about anxiety and memory was found. Objective: The present study examined the anxiolytic and memory enhancing activity of ethanolic extract of V. zizanioides (EEVZ dried roots in mice. Materials and Methods: Activity of EEVZ was assessed using models of anxiety (elevated plus-maze [EPM], light/dark test, hole board test, marble-burying test and learning and memory (EPM, passive shock avoidance paradigm. Results: EEVZ at doses of 100, 200, and 300 mg/kg b.w. illustrated significant anxiolytic activity indicated by increase in time spent and number of entries in open arm, time spent in lightened area, number of head poking and number marble buried when compared to that of diazepam (1 mg/kg b.w., a reference standard. The same treatment showed a significant decrease in transfer latency to reach open arm, shock-free zone, and number of mistakes when compared to that of scopolamine (0.3 mg/kg b.w.. EEVZ in all the doses (100, 200, and 300 mg/kg b.w. significantly decreased mortality in sodium nitrite (250 mg/kg b.w. induced hypoxia and also significantly increases contraction induced by acetylcholine on rat ileum preparation. Conclusion: The result emanated in the present investigation revealed EEVZ possesses significant anxiolytic and nootropic activity by possibly interplaying with neurotransmitters implicated in anxiety and learning and memory.

  6. Anxiolytic effects of orcinol glucoside and orcinol monohydrate in mice.

    Science.gov (United States)

    Wang, Xiaohong; Li, Guiyun; Li, Peng; Huang, Linyuan; Huang, Jianmei; Zhai, Haifeng

    2015-06-01

    Anxiety is a common psychological disorder, often occurring in combination with depression, but therapeutic drugs with high efficacy and safety are lacking. Orcinol glucoside (OG) was recently found to have an antidepressive action. To study the therapeutic potential of OG and orcinol monohydrate (OM) as anxiolytic agents. Anxiolytic effects in mice were measured using the elevated plus-maze, hole-board, and open-field tests. Eight groups of mice were included in each test. Thirty minutes before each test, mice in each group received one oral administration of OG (5, 10, or 20 mg/kg), OM (2.5, 5, or 10 mg/kg), the positive control diazepam (1 or 5 mg/kg), or control vehicle. Each mouse underwent only one test. Uptake of orcinol (5 mg/kg) in the brain was qualitatively detected using the HPLC-MS method. OG (5, 10, and 20 mg/kg) and OM (2.5 and 5 mg/kg) increased the time spent in open arms and the number of entries into open arms in the elevated plus-maze test. OG (5 and 10 mg/kg) and OM (2.5 and 5 mg/kg) increased the number of head-dips in the hole-board test. At all tested doses, OG and OM did not significantly affect the locomotion of mice in the open-field test. Orcinol could be detected in the mouse brain homogenates 30 min after oral OM administration, having confirmed that OM is centrally active. The results demonstrated that OG and OM are anxiolytic agents without sedative effects, indicating their therapeutic potential for anxiety.

  7. Association of ABCB1 polymorphisms with the antiemetic efficacy of granisetron plus dexamethasone in breast cancer patients.

    Science.gov (United States)

    Tsuji, Daiki; Kim, Yong-Il; Nakamichi, Hidenori; Daimon, Takashi; Suwa, Kaori; Iwabe, Yutaro; Hayashi, Hideki; Inoue, Kazuyuki; Yoshida, Masayuki; Itoh, Kunihiko

    2013-01-01

    Resistance to antiemetic treatment with 5-hydroxytryptamine 3 receptor antagonists is a problem, with 20-30% of patients showing unsatisfactory responses. Efflux transport by P-glycoprotein, encoded by the ATP-binding cassette ABCB1 gene in the blood-brain barrier, has been the suggested resistance mechanism. We evaluated the association between the antiemetic efficacy of granisetron plus dexamethasone and ABCB1 polymorphisms 3435C>T and 2677G>T/A. Sixty-four breast cancer patients treated with doxorubicin plus cyclophosphamide were evaluated for their responses to antiemetic therapy. Genotyping of patient DNA samples for ABCB1 single nucleotide polymorphisms was performed; the genotypes were then investigated for their association with the efficacy of prophylactic antiemetics. The acute phase complete response rate was 83% in GG subjects (n = 12), and 69% (n = 35) and 41% (n = 17) in heterozygous and homozygous carriers of the 2677T/A allele, respectively (p = 0.047). The ABCB1 2677 TT genotype group showed significantly lower rates of complete control of acute emesis than the group with GG genotypes (p = 0.045). No significant association with complete response was found for 3435C>T (p = 0.190). ABCB1 polymorphisms may influence the extent of acute emesis control in granisetron-treated patients, making the ABCB1 genotype a predictor of prophylactic antiemetic response.

  8. Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla.

    Science.gov (United States)

    Jung, Ji Wook; Ahn, Nam Yoon; Oh, Hye Rim; Lee, Bo Kyung; Lee, Kang Jin; Kim, Sun Yeou; Cheong, Jae Hoon; Ryu, Jong Hoon

    2006-11-24

    The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (Prhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (Prhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.

  9. [Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy].

    Science.gov (United States)

    Yamasaki, Fumiyuki; Watanabe, Yosuke; Nosaka, Ryo; Kenjo, Masahiro; Nakamura, Kazuhiro; Takayasu, Takeshi; Saito, Taiichi; Tominaga, Atsushi; Sugiyama, Kazuhiko; Kurisu, Kaoru

    2014-01-01

    Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. Between December 2011 and January 2013, 34 patients(19 males, 15 females;age range, 3-80 years)received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting(grade 1)or nausea(grade 2)were treated with granisetron as a rescue anti-emetic. Episodes were graded as(1)no vomiting, no nausea, no anti-emetic;(2)no vomiting, nausea, no anti-emetic;(3)no vomiting, nausea with anti-emetic;and(4)vomiting. Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5(55.6%)experienced grade 2 nausea or vomiting. Two of 6 patients(33.3%)treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients(16.7%)who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia(pgranisetron. Four of 9 patients(44.4%)treated with granisetron experienced constipation(grade 1 or 2);its administration had no major adverse effects in our study population. Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation.

  10. Chronic nausea in advanced cancer patients: a retrospective assessment of a metoclopramide-based antiemetic regimen.

    Science.gov (United States)

    Bruera, E; Seifert, L; Watanabe, S; Babul, N; Darke, A; Harsanyi, Z; Suarez-Almazor, M

    1996-03-01

    The purpose of this retrospective study is to assess the frequency and intensity of chronic nausea in patients admitted to the Palliative Care Unit and the results of a metoclopramide-based treatment regimen. We reviewed the medical records of 100 consecutive patients admitted to the Palliative Care Unit at the Edmonton General Hospital until death during 1992-1993. All patients had terminal cancer and normal cognitive function. All patients completed the Functional Analogue Scale for appetite, nausea, pain, activity, shortness of breath, and sensation of well-being at 1000 and 1600 hours every day. Patients who complained of nausea initially received metoclopramide 10 mg every 4 hr orally or subcutaneously (Step 1). If nausea persisted, dexamethasone 10 mg twice daily was added (Step 2). Step 3 consisted of a continuous subcutaneous infusion of metoclopramide of 60-120 mg/day plus dexamethasone. If no response was observed, other antiemetics were administered (Step 4). Upon admission to the unit, 32 patients (32%) presented with nausea. During the average admission of 25 +/- 13 days, 98 patients (98%) developed nausea. Twenty-five patients (25%) required other antiemetics because of bowel obstruction (18), extrapyramidal side effects (3), or other reasons (4). Most patients without bowel obstruction achieved excellent control of nausea using the metoclopramide-based regimen. During the first 5 days and last 5 days of admission, nausea had significantly lower intensity than the rest of the symptoms that were monitored. Our results suggest that, although nausea is very frequent, it can be well controlled in the majority of patients using safe and simple antiemetic regimens.

  11. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models

    Directory of Open Access Journals (Sweden)

    Damião Pergentino de Sousa

    2015-10-01

    Full Text Available The clinical efficacy of standardized essential oils (such as Lavender officinalis, in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity is conducted. The essential oil with the best profile is Lavendula angustifolia, which has already been tested in controlled clinical trials with positive results. Citrus aurantium using different routes of administration also showed significant effects in several animal models, and was corroborated by different research groups. Other promising essential oils are Citrus sinensis and bergamot oil, which showed certain clinical anxiolytic actions; along with Achillea wilhemsii, Alpinia zerumbet, Citrus aurantium, and Spiranthera odoratissima, which, like Lavendula angustifolia, appear to exert anxiolytic-like effects without GABA/benzodiazepine activity, thus differing in their mechanisms of action from the benzodiazepines. The anxiolytic activity of 25 compounds commonly found in essential oils is also discussed.

  12. Intravenous dextrose administration reduces postoperative antiemetic rescue treatment requirements and postanesthesia care unit length of stay.

    Science.gov (United States)

    Dabu-Bondoc, Susan; Vadivelu, Nalini; Shimono, Chantelle; English, Annette; Kosarussavadi, Boonsri; Dai, Feng; Shelley, Kirk; Feinleib, Jessica

    2013-09-01

    Postoperative nausea and vomiting (PONV) remains the most common postoperative complication, and causes decreased patient satisfaction, prolonged postoperative hospital stays, and unanticipated admission. There are limited data that indicate that dextrose may reduce nausea and vomiting. In this trial, we attempted to determine whether the rate of PONV can be decreased by postoperative administration of IV dextrose bolus. To test the effect of postoperative dextrose administration on PONV rates, we conducted a double-blind, randomized, placebo-controlled trial. We enrolled 62 nondiabetic, ASA class I or II nonsmoking outpatients scheduled for gynecologic laparoscopic and hysteroscopic procedures. Patients were randomized into 2 groups: the treatment group received dextrose 5% in Ringer lactate solution, and the control (placebo) group received Ringer lactate solution given immediately after surgery. All patients underwent a standardized general anesthesia and received 1 dose of antiemetic a half hour before emergence from anesthesia. PONV scores, antiemetic rescue medications, narcotic consumption, and discharge time were recorded in the postanesthesia care unit (PACU) in half-hour intervals. The 2 groups were similar with regard to age, weight, anxiety scores, prior PONV, non per os status, presurgical glucose, anesthetic duration, intraoperative narcotic use, and total weight-based fluid volume received. Postoperative nausea scores were not significantly different in the dextrose group compared with the control group (P > 0.05) after Bonferroni correction for repeated measurements over time. However, patients who received dextrose 5% in Ringer lactate solution consumed less rescue antiemetic medications (ratio mean difference, 0.56; 95% confidence interval, 0.39-0.82; P = 0.02), and had a shorter length of stay in the PACU (ratio mean difference, 0.80; 95% confidence interval, 0.66-0.97; P = 0.03) compared with patients in the control group. In this trial

  13. Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-09-01

    Full Text Available Chemotherapy-induced nausea and vomiting (CINV is a complex pathophysiological condition and consists of two phases. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin (5-HT from the enterochromaffin cells in the gastrointestinal tract (GIT, while the delayed phase is a consequence of release of substance P (SP in the brainstem. However, more recent findings argue against this simplistic neurotransmitter and anatomical view of CINV. Revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P, prostaglandins and related arachidonic acid derived metabolites in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system (ENS [1]. No single antiemetic is currently available to completely prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 receptor antagonist (e.g. aprepitant for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics against different emetogens including cisplatin-induced acute and delayed vomiting, by themselves they are not very effective against CINV in cancer patients. Cannabinoids such as D9-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli as well as being effective against both phases of CINV in animals and patients. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists. Cannabinoids (both phyto-derived and synthetic behave as agonist antiemetics via the activation of cannabinoid CB1 receptors in both the brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist since inverse CB1

  14. Palonosetron-A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

    International Nuclear Information System (INIS)

    Siddiqi, Nasir H.; Khan, Atif J.; Devlin, Phillip M.

    2009-01-01

    Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.

  15. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics

    Directory of Open Access Journals (Sweden)

    May MB

    2016-05-01

    Full Text Available Megan Brafford May,1 Ashley E Glode2 1Department of Pharmacy, Baptist Health Lexington, Lexington, KY, USA; 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: Chemotherapy-induced nausea and vomiting (CINV is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC. The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine. Keywords: dronabinol, cannabinoids, antiemetic, chemotherapy-induced nausea and vomiting

  16. Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study.

    Science.gov (United States)

    Poon, R. T.; Chow, L. W.

    1998-01-01

    A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory. PMID:9635849

  17. Evidence-based recommendations for the use of antiemetics in radiotherapy

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Feyer, Petra Ch.; Molassiotis, Alexander; Rossi, Romina; Clark-Snow, Rebecca A.; Olver, Ian; Warr, David; Schiavone, Concetta; Roila, Fausto

    2005-01-01

    Background and purpose: To report recommendations given in the Multinational Association of Supportive Care in Cancer (MASCC) International Consensus Conference regarding the use of antiemetics in radiotherapy. Patients and methods: A steering committee under MASCC auspice chose panel participants for the guidelines development process on prevention of chemotherapy- and radiotherapy-induced emesis (RIE). Pertinent information from published literature as of March 2004 was reviewed for the guideline process. Both the MASCC level of scientific confidence and level of consensus, and the American Society of Clinical Oncology (ASCO) type of evidence and grade for recommendation were adopted. Results: Total body irradiation is classified at high risk, upper abdomen at moderate, lower thorax, pelvis, cranium (radiosurgery) and craniospinal at low, head and neck, extremities, cranium and breast at minimal risk. The recommendations for the use of antiemetics in radiotherapy are as follows: prophylaxis with a 5-HT3 antagonist in patients at high and moderate risk levels of RIE (±dexamethasone in the former group), prophylaxis or rescue with a 5-HT3 antagonist in the low risk group, and rescue with dopamine or a 5-HT3 receptor antagonist in minimal risk level. Conclusions: These recommendations represent a valid tool for prophylaxis and treatment of RIE in clinical practice

  18. Antiemetic effects of lerisetron in radiation-induced emesis in the dog

    International Nuclear Information System (INIS)

    Gomez-de-Segura, I.A.; De Miguel, E.; Grande, A.G.

    1998-01-01

    The 5-HT 3 receptor antagonists are the most potent antiemetics known at present. Lerisetron is a new 5-HT 3 receptor antagonist chemically unrelated to other antagonists like Ondansetron. An emesis model in the dog induced by irradiation with 60 Co was used, and 8 Gy were administered over the total body surface. An irradiated control group was established and received no medication, and two irradiated groups received treatment with either Ondansetron or Lerisetron. The 'up-down' technique was employed to determine the effective dose (ED 50 ). A logarithmic scale was used to increase or decrease the doses in each case. The initial doses were 300 μg/kg for Ondansetron and 100 μg/kg for Lerisetron. All animals in the control group vomited. The ED 50 of Ondansetron was 178 ± 151 μg/kg body wt and that of Lerisetron was 63 ± 18 μg/kg. Lerisetron is more potent and presented less individual variability than Ondansetron, but its antiemetic effects were equally effective. (orig.)

  19. GABAergic anxiolytic drug in water increases migration behaviour in salmon

    Science.gov (United States)

    Hellström, Gustav; Klaminder, Jonatan; Finn, Fia; Persson, Lo; Alanärä, Anders; Jonsson, Micael; Fick, Jerker; Brodin, Tomas

    2016-12-01

    Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.

  20. Anxiolytic Effect of Aromatherapy Massage in Patients with Breast Cancer

    Science.gov (United States)

    Kuriyama, Hiroko; Shigemori, Ichiro; Watanabe, Satoko; Aihara, Yuka; Kita, Masakazu; Sawai, Kiyoshi; Nakajima, Hiroo; Yoshida, Noriko; Kunisawa, Masahiro; Kawase, Masanori; Fukui, Kenji

    2009-01-01

    We examined how aromatherapy massage influenced psychologic and immunologic parameters in 12 breast cancer patients in an open semi-comparative trial. We compared the results 1 month before aromatherapy massage as a waiting control period with those during aromatherapy massage treatment and 1 month after the completion of aromatherapy sessions. The patients received a 30 min aromatherapy massage twice a week for 4 weeks (eight times in total). The results showed that anxiety was reduced in one 30 min aromatherapy massage in State-Trait Anxiety Inventory (STAI) test and also reduced in eight sequential aromatherapy massage sessions in the Hospital Anxiety and Depression Scale (HADS) test. Our results further suggested that aromatherapy massage ameliorated the immunologic state. Further investigations are required to confirm the anxiolytic effect of aromatherapy in breast cancer patients. PMID:18955225

  1. Anxiolytic Effect of Aromatherapy Massage in Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jiro Imanishi

    2009-01-01

    Full Text Available We examined how aromatherapy massage influenced psychologic and immunologic parameters in 12 breast cancer patients in an open semi-comparative trial. We compared the results 1 month before aromatherapy massage as a waiting control period with those during aromatherapy massage treatment and 1 month after the completion of aromatherapy sessions. The patients received a 30 min aromatherapy massage twice a week for 4 weeks (eight times in total. The results showed that anxiety was reduced in one 30 min aromatherapy massage in State-Trait Anxiety Inventory (STAI test and also reduced in eight sequential aromatherapy massage sessions in the Hospital Anxiety and Depression Scale (HADS test. Our results further suggested that aromatherapy massage ameliorated the immunologic state. Further investigations are required to confirm the anxiolytic effect of aromatherapy in breast cancer patients.

  2. Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis

    OpenAIRE

    Ho, Robin S. T.; Chung, Vincent C. H.; Wong, Charlene H. L.; Wu, Justin C. Y.; Wong, Samuel Y. S.; Wu, Irene X. Y.

    2017-01-01

    Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from ...

  3. Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.

    Science.gov (United States)

    Chouinard, G; Lefko-Singh, K; Teboul, E

    1999-08-01

    1. The benzodiazepines are among the most frequently prescribed of all drugs and have been used for their anxiolytic, anticonvulsant, and sedative/hypnotic properties. Since absorption rates, volumes of distribution, and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. The importance of alpha and beta half-lives in the actions of benzodiazepines is discussed. 2. The role of cytochrome P450 isozymes in the metabolism of benzodiazepines and in potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs is discussed. 3. Buspirone, an anxiolytic with minimal sedative effects, undergoes extensive metabolism, with hydroxylation and dealkylation being the major pathways. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. 4. Zopiclone and zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, and decarboxylation of zopiclone occur, and zolpidem undergoes oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring system. Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics. Metabolic drug-drug interactions have been reported with zopiclone and erythromycin, trimipramine, and carbamazepine. Reports to date indicate minimal interactions of zolpidem with coadministered drugs; however, it has been reported to affect the Cmax and clearance of chlorpromazepine and to decrease metabolism of the antiviral agent ritonavin. Since CYP3A4 has been reported to play an important role in metabolism of zolpidem, possible interactions with drugs which are substrates and/or inhibitors of that CYP isozyme should be considered.

  4. Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

    Science.gov (United States)

    Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit

    2015-12-01

    Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

  5. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Paul J. Hesketh

    2015-01-01

    Full Text Available Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA, netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  6. Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.

    Science.gov (United States)

    Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo

    2016-05-01

    Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Toxicity and Anxiolytic Property of Nettle in Mice in Light/Dark Test

    OpenAIRE

    Doukkali Z; Taghzouti K; Bouidida El H; Kamal R; El Jemeli M; Bahia B; Zellou A; Cherrah Y; Alaoui K

    2016-01-01

    Background: Anxiety is an unpleasant state of inner turmoil often accompanied by cognitive, somatic, emotional, and behavioral components. There is some evidence in traditional medicine for the effectiveness of Urtica urens in the treatment of anxiety in humans. The present study was designed to study anxiolytic property of aqueous extracts of Urtica urens; an important and commonly used for its medicinal properties belongs to urticaceae family. Methods: The anxiolytic activity was evaluated ...

  8. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.

    Science.gov (United States)

    Hsu, Eric S

    2010-01-01

    Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.

  9. Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.

    Science.gov (United States)

    Natale, James J

    2015-01-01

    This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

  10. Anxiolytic effect of clonazepam in female rats: grooming microstructure and elevated plus maze tests.

    Science.gov (United States)

    Nin, Maurício S; Couto-Pereira, Natividade S; Souza, Marilise F; Azeredo, Lucas A; Ferri, Marcelo K; Dalprá, Walesca L; Gomez, Rosane; Barros, Helena M T

    2012-06-05

    Grooming behavior is an adaptation to a stressful environment that can vary in accordance with stress intensity. Direct and indirect GABA(A) receptor agonists decrease duration, frequency, incorrect transitions and uninterrupted bouts of grooming. Hormonal variation during the different phases of the estrous cycle of female rats also changes the grooming behavior. It is known that GABA(A) agonists and endogenous hormones change anxiety-like behaviors observed in the elevated plus maze test, a classical animal model of anxiety. This study was designed to determine the anxiolytic effect of clonazepam in female rats in different estrous phases and to correlate anxiety behaviors in the elevated plus maze and grooming microstructure tests. Our results show that female rats displayed higher anxiety-like behavior scores during the estrus and proestrus phases in the elevated plus maze and that clonazepam (0.25 mg/kg; i.p.) had an anxiolytic effect that was independent of the estrous phase. Grooming behaviors were higher in the proestrus phase but were decreased by clonazepam administration, independent of the estrous phase, demonstrating the anxiolytic effect of this drug in both animal models. Grooming behaviors were moderately associated with anxiolytic-like behaviors in the elevated plus maze test. Here, we describe the anxiolytic effect of clonazepam and the influence of estrous phase on anxiety. Moreover, we show that the grooming microstructure test is a useful tool for detecting anxiolytic-like behaviors in rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Subtypes of adolescent sedative/anxiolytic misusers: A latent profile analysis.

    Science.gov (United States)

    Hall, Martin T; Howard, Matthew O; McCabe, Sean Esteban

    2010-10-01

    Few empirically-based taxonomies of nonmedical prescription drug misusers have been published. This study used latent profile analysis (LPA) to identify classes of adolescent sedative/anxiolytic misusers. Interviews assessing substance use, psychiatric symptoms, antisocial traits/behavior, and traumatic life experiences were conducted with 723 Missouri youth in residential care for antisocial behavior. Sedative/anxiolytic misusers (N=247) averaged 15.8 (S.D.=1.1) years of age; a majority were male (83.8%), White (70.0%), and resided in rural/small town areas (53.8%). LPA yielded a three-class solution. Class 1 (59.1%) was comprised of youth with significantly lower levels of currently distressing psychiatric symptoms, fewer lifetime traumatic experiences, less problematic substance use histories, less frequent antisocial behavior, and less impulsivity than youth in Classes 2 and 3. Class 2 (11.3%) youth had high levels of currently distressing psychiatric symptoms and more frequent antisocial behavior compared to youth in Classes 1 and 3. Class 3 (29.5%) youth evidenced levels of psychiatric and behavioral problems that were intermediate to those of Class 1 and 2 youth. Frequency of sedative/anxiolytic misuse was significantly higher in Classes 2 and 3 compared to Class 1. Members of Class 2 and Class 3 also had the highest levels of psychiatric symptoms for which sedatives/anxiolytics are commonly prescribed. Significant differences between classes were observed across a range of health, mental health, personality, and behavioral variables. Adolescents who misused prescription sedatives/anxiolytics evidenced significant heterogeneity across measures of psychiatric and behavioral dysfunction. Youth with comparatively high levels of anxiety and depression reported significantly more intensive sedative/anxiolytic misuse than their counterparts and may be at high risk for sedative/anxiolytic abuse and dependence. 2010 Elsevier Ltd. All rights reserved.

  12. The psychopharmacological activities of Vietnamese ginseng in mice: characterization of its psychomotor, sedative–hypnotic, antistress, anxiolytic, and cognitive effects

    Directory of Open Access Journals (Sweden)

    Irene Joy I. dela Peña

    2017-04-01

    Conclusion: VG, like other ginseng products, has significant and potentially useful psychopharmacological effects. This includes, but is not limited to, psychomotor stimulation, anxiolytic, antistress, and memory enhancing effects.

  13. Diclofenac with or without an antiemetic for acute migraine headaches in adults

    Science.gov (United States)

    Derry, Sheena; Rabbie, Roy; Moore, R Andrew

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter (OTC) analgesics. Diclofenac is an established analgesic, and new formulations using the potassium or epolamine salts, which can be dissolved in water, have been developed for rapid absorption, which may be beneficial in acute migraine. Co-therapy with an antiemetic should help to reduce the nausea and vomiting commonly associated with migraine. Objectives To determine the efficacy and tolerability of diclofenac, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and reference lists for studies through 27 September 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using self administered diclofenac to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Five studies (1356 participants) compared oral diclofenac with placebo, and one also compared it with sumatriptan; none combined diclofenac with a self administered antiemetic. Four studies treated attacks with single doses of medication, and two allowed an optional second dose for inadequate response. Only two studies, with three active treatment arms, provided data for pooled analysis of primary outcomes. For single doses of diclofenac

  14. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

    Science.gov (United States)

    Derry, Sheena; Moore, R Andrew

    2013-04-30

    This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010 for the original review, and to 13 February 2013 for the update. Two clinical trials registers (ClinicalTrials.gov and gsk-clinicalstudyregister.com) were also searched on both occasions. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared with placebo or other active treatment. Searches for the update identified one additional study for inclusion. Eleven studies (2942 participants, 5109 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12 (19% response with paracetamol, 10% with placebo), 5.0 (56% response with paracetamol, 36% with placebo) and 5.2 (39% response with paracetamol, 20% with placebo) for 2-hour pain-free and 2- and 1

  15. Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic.

    Science.gov (United States)

    Sanger, D J; Zivkovic, B

    1994-01-01

    Alpidem in an imidazopyridine derivative which binds selectively to the omega 1 (BZ1) receptor subtype. It is active in some, but not all, behavioural tests sensitive to benzodiazepine anxiolytics and has clinical anti-anxiety effects. However, in a previous study, it was shown that alpidem did not substitute for chlordiazepoxide in rats trained to discriminate this benzodiazepine. The present experiments were carried out to investigate the discriminative stimulus properties of alpidem in greater detail. In the first experiment rats learned to discriminate a dose of 10 mg/kg alpidem from saline. Acquisition of the discrimination was long and performance unstable. Chlordiazepoxide, clorazepate and zolpidem substituted only partially for alpidem but the effects of the training dose of alpidem were blocked by 10 mg/kg flumazenil. The second experiment established stimulus control more rapidly to a dose of 30 mg/kg alpidem. Alpidem induced dose-related stimulus control, and dose-related and complete substitution for alpidem was produced by zolpidem, abecarnil, CL 218,872, triazolam and suriclone. Partial substitution occurred with chlordiazepoxide, clorazepate and pentobarbital. In most cases, high levels of substitution were produced only by doses which greatly reduced response rates even though the training dose of alpidem produced only modest decreases in rates. Ethanol, buspirone and bretazenil produced very little substitution for alpidem and both flumazenil and bretazenil antagonised the effects of alpidem. In two further experiments alpidem was found to substitute for the stimulus produced by zolpidem (2 mg/kg) but not for that produced by ethanol (1.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. The failure of anxiolytic therapies in early clinical trials: what needs to be done.

    Science.gov (United States)

    Stewart, Adam Michael; Nguyen, Michael; Poudel, Manoj K; Warnick, Jason E; Echevarria, David J; Beaton, Elliott A; Song, Cai; Kalueff, Allan V

    2015-04-01

    Anxiety spectrum disorders (ASDs) are highly prevalent psychiatric illnesses that affect millions of people worldwide. Strongly associated with stress, common ASDs include generalized anxiety disorder, panic, social anxiety, phobias and drug-abuse-related anxiety. In addition to ASDs, several other prevalent psychiatric illnesses represent trauma/stressor-related disorders, such as post-traumatic stress disorder and acute stress disorder. Anxiolytic drugs, commonly prescribed to treat ASDs and trauma/stressor-related disorders, form a highly heterogenous group, modulating multiple neurotransmitters and physiological mechanisms. However, overt individual differences in efficacy and the potential for serious side-effects (including addiction and drug interaction) indicate a need for further drug development. Yet, over the past 50 years, there has been relatively little progress in the development of novel anxiolytic medications, especially when promising candidate drugs often fail in early clinical trials. Herein, the authors present recommendations of the Task Force on Anxiolytic Drugs of the International Stress and Behavior Society on how to improve anxiolytic drug discovery. These recommendations cover a wide spectrum of aspects, ranging from methodological improvements to conceptual insights and innovation. In order to improve the success of anxiolytic drugs in early clinical trials, the goals of preclinical trials may need to be adjusted from a clinical perspective and better synchronized with those of clinical studies. Indeed, it is important to realize that the strategic goals and approaches must be similar if we want to have a smoother transition between phases.

  17. Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Behnam Motlagh, P. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Henriksson, R. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Grankvist, K. [Dept. of Clinical Chemistry, Umeaa Univ. Hospital (Sweden)

    1995-12-31

    At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, so far as we know, not been studied in this respect. In the present study, the effects of the 5-HT{sub 3} receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10{sup -5} mol/l) had no effect on the survival of irradiated cells. Granisetron (10{sup -5} mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10{sup -7} mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT{sub 3} receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment. (orig.).

  18. Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro

    International Nuclear Information System (INIS)

    Behnam Motlagh, P.; Henriksson, R.; Grankvist, K.

    1995-01-01

    At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, so far as we know, not been studied in this respect. In the present study, the effects of the 5-HT 3 receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10 -5 mol/l) had no effect on the survival of irradiated cells. Granisetron (10 -5 mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10 -7 mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT 3 receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment. (orig.)

  19. Prophylactic antiemetic effects of midazolam, dexamethasone, and its combination after middle ear surgery

    International Nuclear Information System (INIS)

    Makhdoom, Naeem K; Farid, Magdy F

    2009-01-01

    To evaluate and compare the efficacy of the combination of midazolam and dexamethasone, with midazolam and dexamethasone alone, for the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing middle ear surgery. A prospective, randomized, double-blind, placebo-controlled study in 80 female patients (mean age 32.6 years), undergoing middle ear surgery with general anesthesia at Ohud Hospital, Madina, Kingdom of Saudi Arabia from May 2007 to May 2008. Patients were classified into 4 groups. They received intravenous normal saline (S group), midazolam 0.075 mg/kg (M group), or dexamethasone 10 mg (D group), or a combination of midazolam and dexamethasone (MD group), before the induction of anesthesia. Postoperatively for 24 hours observation and assessment of nausea, vomiting, rescue anti-emetics, and side effects of the study drugs such as headache and drowsiness were carried out. There was a significant difference between the 4 groups. The MD group was the least to develop PONV compared to other groups (p<0.01). Regarding nausea, there was a non-significant difference between the 4 groups, although the MD group developed the least symptoms among the 4 groups, there were no significant differences in pain intensity and side effects such as, headache, dizziness, and drowsiness between the 4 groups. The combination of midazolam 0.075 mg/kg and dexamethasone 10 mg intravenously is better than either drug alone in reducing the incidence of PONV in female patients after middle ear surgery. (author)

  20. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    Directory of Open Access Journals (Sweden)

    Mohd Nauman Saleem

    2016-01-01

    Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

  1. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics

    International Nuclear Information System (INIS)

    May, Megan Brafford; Glode, Ashley E

    2016-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine

  2. Palonosetron as an anti-emetic and anti-nausea agent in oncology.

    Science.gov (United States)

    Aapro, Matti S

    2007-12-01

    Palonosetron (Aloxi(®), Onicit(®), Paloxi(®)) is a second-generation 5-HT(3) receptor antagonist (RA) with an extended half-life of ~40 hours and high binding affinity for the 5-HT₃ receptor that is markedly different from other 5-HT(3) RAs. Phase III trials demonstrate that a single dose of palonosetron compared with traditional 5-HT₃ RAs is more effective in preventing chemotherapy-induced nausea and vomiting (CINV) during the first 24 hours following chemotherapy (acute CINV), and also exhibits prolonged efficacy to provide significantly better protection from CINV in the delayed and overall phases. This superior and extended protection from CINV conferred by palonosetron following a single intravenous dose before chemotherapy simplifies dosing schedules. Recent research has focused on optimization of palonosetron-based antiemetic regimens, particularly in combination with steroids and neurokinin-1 RAs. The available clinical data indicate high control rates for palonosetron, suggesting a synergistic potential for protection in patients scheduled to receive emetogenic drug regimens.

  3. Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.

    Science.gov (United States)

    Uchida, Masayuki; Kobayashi, Orie; Shimizu, Kimiko

    2017-01-01

    Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1- 13 C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

  4. The anxiolytic effect of Juniperus virginiana L. essential oil and determination of its active constituents.

    Science.gov (United States)

    Zhang, Kai; Yao, Lei

    2018-05-15

    Essential oil from Juniperus virginiana L. (eastern red cedarwood essential oil, CWO) has been used to relax mind and enhance comfort for medical purposes. Few reports showed its effect on anxiety behaviors in animal models. The present study investigated the anxiolytic effect of CWO using two anxiety tests in mice, then determined the major active constituents, examined the change of neurotransmitters after intraperitoneal (i.p.) administration. Analysis using GC/MS revealed that the CWO contained (-)-α-cedrene (28.11%), (+)-β-cedrene (7.81%), (-)-thujopsene (17.71%) and (+)-cedrol (24.58%). CWO at 400-800mg/kg increased the percentage of open arm entries and the percentage of the time spent in open arms in the elevated plus maze (EPM), suggesting that the oil has anxiolytic effect. However, it didn't show anxiolytic effect in the light-dark box (LDB) test. Tests of the cedrene did not show anxiolytic effect in either test, but rather induced anxiety-related behaviors and inhibited the locomotor activity in EPM and LDB. Cedrol produced significant anxiolytic effect in both EPM and LDB tests at 400-1600mg/kg and 800-1600mg/kg, respectively. A more significant increase in locomotor activity was observed in cedrol at 200-1600mg/kg administration than CWO. CWO increased the 5-hydroxytryptamine (5-HT) concentration at 800mg/kg, whereas it didn't affect the dopamine (DA) concentration. Cedrol significantly reduced the DA level at 100-200mg/kg and elevated the 5-HT level at 1200-1600mg/kg. Moreover, it changed the ratio of 5-hydroxyindoleacetic acid/5-HT and 3, 4-dihydroxyphenyl acetic acid/DA at 1200-1600mg/kg. CWO and cedrol, in particular might act in an anxiolytic effect through the 5-HTnergic and DAnergic pathways. Copyright © 2018. Published by Elsevier Inc.

  5. Anxiolytic-like effects of alverine citrate in experimental mouse models of anxiety.

    Science.gov (United States)

    Gupta, Deepali; Radhakrishnan, Mahesh; Kurhe, Yeshwant

    2014-11-05

    Anxiety disorders are widely spread psychiatric illnesses that are a cause of major concern. Despite a consistent increase in anxiolytics, the prevalence of anxiety is static; this necessitates the development of new compounds with potential activity and minimum unwanted effects. A serotonergic (5HT) system plays an important role in pathogenesis of anxiety and predominantly involves 5HT1A receptor action in mediating anxiety-like behavior; the antagonism of 5HT1A receptor has demonstrated to produce anxiolytic-like effects. Alverine citrate (AVC) is reported as a 5HT1A antagonist; however, its effects on anxiety-like behavior are not investigated. Thus, the present study, by utilizing a neurobehavioral approach, examined the anxiolytic-like effects of AVC in experimental mouse models of anxiety. Mice were acutely treated with AVC (5-20mg/kg, i.p.)/diazepam (DIA, 2mg/kg, i.p.) and subjected to four validated anxiety models viz. elevated plus-maze (EPM), light/dark (L/D), hole-board (HB) and marble burying (MB) tests. AVC (15-20mg/kg) and DIA significantly increased open arm activity in EPM, exploration in light chamber in L/D test, exploratory behavior in HB and reduced MB behavior in marble burying test. AVC (5mg/kg) had no effect on all behavioral tests, while AVC (10mg/kg) produced partial effects. It revealed anxiolytic-like effects of AVC. Furthermore, anxiolytic-like effects of AVC at higher doses (15-20mg/kg) were more pronounced than lower doses (10mg/kg) and were quite similar to the standard drug DIA. The present finding demonstrates, for the first time, the anxiolytic-like effects of AVC, which may be an alternative approach for management of anxiety-related disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 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.

  7. A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

    Science.gov (United States)

    Sanchez-Ledesma, M J; López-Olaondo, L; Pueyo, F J; Carrascosa, F; Ortega, A

    2002-12-01

    In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.

  8. Anxiolytics may promote locomotor function recovery in spinal cord injury patients

    Directory of Open Access Journals (Sweden)

    Pierre A Guertin

    2008-09-01

    Full Text Available Pierre A GuertinNeuroscience Unit, Laval University Medical Center (CHUL, Quebec City, CanadaAbstract: Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI. Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR ligands such as 5-HTR1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously, some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx rodents. Using ‘knock-out’ mice (eg, 5-HTR7-/- and selective antagonists, it has been clearly established that both 5-HTR1A and 5-HTR7 were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR1A agonist in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.Keywords: 5-HT agonists, anxiolytics, locomotion, SCI

  9. Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists

    International Nuclear Information System (INIS)

    Dunn, R.W.; Corbett, R.; Martin, L.L.; Payack, J.F.; Laws-Ricker, L.; Wilmot, C.A.; Rush, D.K.; Cornfeldt, M.L.; Fielding, S.

    1990-01-01

    Antagonists at excitatory amino acid receptors, especially the N-methyl-d-aspartate (NMDA) subtype, have been shown to possess anticonvulsant and anxiolytic properties. Two closely related benzeneethanamines, are potential novel anxiolytic agents which bind with high affinity to the NMDA receptor at the non-competitive site and are relatively non-toxic (LD50's-160 mg/kg, ip). 7189 and 8319 showed anxiolytic effects in schedule controlled conflict assays as well as in the social interaction (SI) and elevated plus maze (EPM) procedures in rats. Following intraperitoneal administration of 7189 at 20 to 60 mg/kg, conflict responding was increased from 2- to 7-fold in the modified Cook and Davidson and Geller conflict paradigms. 8319, at 2.5 to 5 mg/kg, produced a two fold increase in conflict responding. In the non-schedule controlled procedures, 7189 at 20 mg/kg increased SI time by 23% while in the EPM at 10 to 20 mg/kg, open arm exploration time increased by 41 to 77%. Likewise, 8319 at 2.5 and 5 mg/kg increased open arm exploration and SI time by 50 and 37%, respectively. In summary, 7189 and 8319 were efficacious in four behavioral procedures predictive of potential anxiolytic agents. Although these compounds have not been submitted for clinical evaluation, they may represent a new class of beneficial compounds for the treatment of anxiety

  10. Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

    Science.gov (United States)

    Malik, Jai; Karan, Maninder; Vasisht, Karan

    2011-12-01

    Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

  11. CT-Screening for lung cancer does not increase the use of anxiolytic or antidepressant medication

    DEFF Research Database (Denmark)

    Kaerlev, Linda; Iachina, Maria; Pedersen, Jesper Holst

    2012-01-01

    CT screening for lung cancer has recently been shown to reduce lung cancer mortality, but screening may have adverse mental health effects. We calculated risk ratios for prescription of anti-depressive (AD) or anxiolytic (AX) medication redeemed at Danish pharmacies for participants in The Danish...... Lung Cancer Screening Trial (DLCST)....

  12. Anxiolytic-like and sedative effects of Hydrocotyle umbellata L., Araliaceae, extract in mice

    Directory of Open Access Journals (Sweden)

    Fábio F. Rocha

    2011-02-01

    Full Text Available The plant Hydrocotyle umbellata L., Araliaceae (water pennywort, is widely used in Brazilian folk medicine to reduce anxiety. This work investigates the anxiolytic-like effects of the ethanol extract from H. umbellata subterraneous parts as well as the extract's other putative central nervous system effects that could justify its common use. Oral dosing of the extract (0.3 and 1 g/kg clearly showed an anxiolytic-like profile in the elevated plus maze test where it increased the percentage of entries into and the time spent in the open arms of the maze. In the marble-burying test, the extract induced anxiolytic-like effects only at a dose of 1 g/kg, which also causes mild sedative properties in other models. The sedated state was characterized by a slight reduction in spontaneous exploratory activity during the open field test and a potentiating of pentobarbital-induced hypnosis. No signs of motor impairment were detected in the rota rod or chimney tests. The extract did not show antidepressant properties in mice as assessed by the forced swimming test. These results support the use of H. umbellata in Brazilian folk medicine as an anxiolytic and contribute to the scientific knowledge of this possible phytotherapeutic resource.

  13. Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

    Science.gov (United States)

    Ullah, Ihsan; Subhan, Fazal; Ayaz, Muhammad; Shah, Rehmat; Ali, Gowhar; Haq, Ikram Ul; Ullah, Sami

    2015-02-26

    Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation

  14. Study of inclusion complex formation between chlorpromazine hydrochloride, as an antiemetic drug, and β-cyclodextrin, using conductometric technique

    International Nuclear Information System (INIS)

    Rafati, Amir Abbas; Hamnabard, Nazanin; Ghasemian, Ensieh; Nojini, Zabiolah Bolboli

    2009-01-01

    The behavior of micellization of chlorpromazine hydrochloride (CPH) as an antiemetic drug and its inclusion complex formation with β-cyclodextrin (β-CD) was studied using conductometric technique. The binding or association constant of the complexation equilibrium is evaluated from conductometric measurements by using a nonlinear regression method. The resulting K values for micellization as well as complexation are analyzed. The experiments were carried out at different temperatures. It has been found that CPH form only the 1:1 complex. The association constant values are used for evaluation of thermodynamic parameters of complexation, such as ΔG complex o , ΔH complex o and ΔS complex o .

  15. Evaluating the antiemetic administration consistency to prevent chemotherapy-induced nausea and vomiting with the standard guidelines: a prospective observational study.

    Science.gov (United States)

    Vazin, Afsaneh; Eslami, Davood; Sahebi, Ebrahim

    2017-01-01

    Nausea and vomiting (NV) are the most prevalent adverse effects of chemotherapy (CT). This study was conducted to evaluate adherence of the health care team to standard guidelines for antiemetics usage to prevent acute chemotherapy-induced nausea and vomiting (CINV) in a large CT center. A prospective study was performed during an 11-month period on patients receiving CT. A form was designed to collect patients' demographic information and their chemotherapeutic and antiemetic regimen data. The Likert scale was used to measure the effectiveness of the antiemetics in patients. In this study, the effect of patient-related risk factors on the incidence rate of CINV was examined. Based on the results, CINV events were reported by 74.4% of patients. The antiemetic regimen of 71.2% of the patients complied with the guidelines. The complete response, complete protection, and complete control end points did not differ significantly between patients undergoing guidelines-consistent prophylaxis or guidelines-inconsistent prophylaxis. The females clearly showed a higher incidence rate of CINV ( P =0.001) during the first course of CT ( P =0.006). A history of motion sickness did not affect the incidence of NV. The maximum compliance error occurred for the use of aprepitant, as 16.16% of the patients who were receiving aprepitant did not comply with its instructions. The results of this study highlight how CINV was controlled in this center, which was significantly lower than that of the global standard. Perhaps, factors such as noncompliance to antiemetic regimens with standard guidelines and the failure to adhere to the administration instructions of the antiemetics were involved in the incomplete control of CINV.

  16. The cost of antiemetic therapy for chemotherapy-induced nausea and vomiting in patients receiving platinum-containing regimens in daily practice in Japan: a retrospective study.

    Science.gov (United States)

    Hamada, Shota; Hinotsu, Shiro; Hori, Katsuhito; Furuse, Hiroshi; Oikawa, Takehiro; Kawakami, Junichi; Ozono, Seiichiro; Akaza, Hideyuki; Kawakami, Koji

    2012-04-01

    The objective of this study was to estimate the cost of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in daily practice in Japan. This was a retrospective observational study using medical records. Eligible patients were those with bladder or testicular cancer receiving platinum-containing highly emetogenic chemotherapy. The incidence of CINV on days 1-5 in single-day chemotherapy and on days 1-9 in multiple-day chemotherapy, and the costs of antiemetic therapy directly associated with the administration of antiemetics were estimated. The analysis of costs was performed from a hospital perspective. A total of 54 patients or 169 chemotherapy courses were included. In all chemotherapy courses 5-HT(3) receptor antagonists were used on the day(s) that platinum-containing agents were administered and frequently used on subsequent days. In contrast, the use of corticosteroids was infrequent. Acute CINV in single-day chemotherapy was well controlled, but the incidences of delayed CINV in single-day chemotherapy and CINV in multiple-day chemotherapy were relatively high. The costs for antiemetic therapy were $484.65 in courses with CINV and $318.56 in courses without CINV, and the difference was approximately $170 per chemotherapy course, which was considered to be mainly imputable to the prevalence of CINV. The cost of antiemetic therapy for CINV is substantial in Japan as well as in other countries, and it is suggested that the onset of CINV is a possible cost driver. The improvements in antiemetic therapy may contribute not only to improved patient well-being but also to a reduction of economic burden.

  17. 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

  18. Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René

    2014-01-01

    , injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined r....... Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala......AAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests...

  19. Pharmacological evaluation of anxiolytic property of aqueous root extract of Cymbopogon citratus in mice

    Directory of Open Access Journals (Sweden)

    David Arome

    2014-01-01

    Full Text Available Aim: This study was designed to evaluate the anxiolytic property of aqueous root extract of Cymbopogon citratus in mice. Materials and Methods: In this study, stress induced hyperthermia (SIH, elevated plus maze (EPM and open field experimental models were employed. Results: In SIH model, the extract caused a significant (P 0.05 effect. In open field model, 200 mg/kg and 600 mg/kg extract doses significantly (P < 0.05 increased locomotion of the mice more than the standard, while rearing and defecation were less in the extract groups. Conclusion: In different experimental models used significant anxiolytic effect was observed of the aqueous extract at different dose levels in comparison to reference standard and normal saline group. This clearly justified its folkloric application in the treatment of anxiety disorders.

  20. Participation of GABAA Chloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture

    Directory of Open Access Journals (Sweden)

    Juan Francisco Rodríguez-Landa

    2013-01-01

    Full Text Available Human amniotic fluid and a mixture of eight fatty acids (FAT-M identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg% produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement of γ-aminobutyric acid-A (GABAA receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, three GABAA receptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg, GABAA benzodiazepine antagonist flumazenil (5 mg/kg, and noncompetitive GABAA chloride channel antagonist picrotoxin (1 mg/kg. The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. The GABAA antagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects through GABAA receptor chloride channels.

  1. Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect of agmatine in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Kotagale, Nandkishor R; Gawande, Dinesh Y; Bharne, Ashish P; Chopde, Chandrabhan T; Kokare, Dadasaheb M

    2014-06-01

    In the present study, modulation of anxiolytic action of agmatine by neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and 1.2µmol/rat), NPY (10 and 20pmol/rat) or NPY Y1/Y5 receptors agonist [Leu(31), Pro(34)]-NPY (30 and 60pmol/rat) significantly increased the number of punished drinking licks following 15min of treatment. Combination treatment of subeffective dose of NPY (5pmol/rat) or [Leu(31), Pro(34)]-NPY (15pmol/rat) and agmatine (0.3µmol/rat) produced synergistic anxiolytic-like effect. However, intra-CeA administration of selective NPY Y1 receptor antagonist, BIBP3226 (0.25 and 0.5mmol/rat) produced anxiogenic effect. In separate set of experiment, pretreatment with BIBP3226 (0.12mmol/rat) reversed the anxiolytic effect of agmatine (0.6µmol/rat). Furthermore, we evaluated the effect of intraperitoneal injection of agmatine (40mg/kg) on NPY-immunoreactivity in the nucleus accumbens shell (AcbSh), lateral part of bed nucleus of stria terminalis (BNSTl) and CeA. While agmatine treatment significantly decreased the fibers density in BNSTl, increase was noticed in AcbSh. In addition, agmatine reduced NPY-immunoreactive cells in the AcbSh and CeA. Immunohistochemical data suggest the enhanced transmission of NPY from the AcbSh and CeA. Taken together, this study suggests that agmatine produced anxiolytic effect which might be regulated via modulation of NPYergic system particularly in the CeA. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  2. [Trends in the consumption of anxiolytic and hypnotic drugs in a Colombian population].

    Science.gov (United States)

    Machado-Alba, Jorge Enrique; Alzate-Carvajal, Verónica; Jimenez-Canizales, Carlos Eduardo

    2015-01-01

    In Latin America, psychotropic medications are the third most marketed drug group, especially antidepressants (35%) and anxiolytics (5%). The objective of this study was to determine the trends in the consumption and the costs of anxiolytic and hypnotic drugs in a population of patients enrolled in the Health System of Colombia. A descriptive, observational study was performed using the data recorded inprescriptions for any anxiolytic or hypnotic drug prescribed to outpatients in the period between January 2008 and December 2013 in a population of 3.5 million people. Sociodemographic, pharmacological variables, overall costs, and cost per thousand inhabitants per day (CHD), were also recorded. The number of patients who received the drugs studied varied from 11,097 to 19,231 between 2008 and 2013. The most used drugs were clonazepam (44.1% of formulations), alprazolam (31.2%), and lorazepam (13.2%). The invoiced value of anxiolytics increased from US$ 207,673.63 in 2008 to US$ 488,977 in 2013, an increase of 135.4%. The CHD was US$ 0.31 for benzodiazepines, and US$ 0.02 for zaleplon, zolpidem and zopiclone (Z drugs) for 2008, and US$ 0.36 and US$ 0.02 in 2013 respectively. The CHD declined after 2010 following the introduction of generic drugs. Patients receiving benzodiazepines in Colombia are mostly women, average age 55 years, with very low frequency in defined daily doses per thousand inhabitants when compared with other countries. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  3. Quality of life and social determinants of anxiolytics and hypnotics use in women in Poland: a population-based study.

    Science.gov (United States)

    Zagozdzon, Pawel; Kolarzyk, Emilia; Marcinkowski, Jerzy T

    2013-05-01

    The majority of studies show a substantially higher consumption of anxiolytics and antidepressants among women than among men and in the age bracket above 45 years. To analyse association between the use of hypnotics/anxiolytics, and various characteristics of Polish women, including health-related quality of life. One thousand, five hundred and sixty (1,560) women aged 45-60 years completed a questionnaire dealing with the use of hypnotics/anxiolytics, demographic characteristics, environmental and work stress exposure, and self-reported quality of life (SF-36 form). The following variables were revealed as the predictors of hypnotic/anxiolytic use on univariate analysis: age; social pension; stress at work and environmental stress; hormone replacement therapy; headache; palpitations; mood swings or increased muscular tension; anger; duration of symptoms longer than one week; consulting a specialist; and low physical and mental health-related quality of life. The significant protective factors included: vocational and tertiary education; job satisfaction; and home as place of rest. The independent predictors of anxiolytic/hypnotic use included consulting a specialist and symptoms lasting more than one week, while job satisfaction and home as place of rest were the independent protective factors. The use of hypnotic/anxiolytic medication is strongly associated with environmental and psychosocial characteristics of women between 40 and 65 years of age.

  4. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    Science.gov (United States)

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-05

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Anxiolytic-Like Actions of Fatty Acids Identified in Human Amniotic Fluid

    Directory of Open Access Journals (Sweden)

    Rosa Isela García-Ríos

    2013-01-01

    Full Text Available Eight fatty acids (C12–C18 were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic-like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic-like effects. Although a trend toward a dose-response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p. in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic-like effects, suggesting similar actions during intrauterine development.

  6. Chemical composition of hydroethanolic extracts from Siparuna guianensis, medicinal plant used as anxiolytics in Amazon region

    Directory of Open Access Journals (Sweden)

    Giuseppina Negri

    2012-10-01

    Full Text Available Siparuna guianensis Aubl., Siparunaceae, is used as anxiolytic plants in folk medicine by South-American indians, "caboclos" and river-dwellers. This work focused the evaluation of phenolic composition of hydroethanolic extract of S. guianensis through HPLC-DAD-ESI/MS/MS. The constituents exhibited protonated, deprotonated and sodiated molecules and the MS/MS fragmentation of protonated, deprotonated and sodiated molecules provided product ions with rich structural information. Vicenin-2 (apigenin-6,8-di-C-glucoside was the main constituent found in S. guianensis together quercetin-3,7-di-O-rhamnoside and kaempferol-3,7di-O-rhamnoside. A commercial extract of Passiflora incarnata (Phytomedicine was used as surrogate standard and also was analyzed through HPLC-DAD-ESI/ MS/MS, showing flavones C-glycosides as constituents, among them, vicenin-2 and vitexin. The main constituent was vitexin. Flavonols triglycosides was also found in low content in S. guianensis and were tentatively characterized as quercetin-3O-rutinoside-7-O-rhamnoside, quercetin-3-O-pentosyl-pentoside-7-O-rhamnoside and kaempferol-3-O-pentosyl-pentoside-7-O-rhamnoside. Apigenin and kaempferol derivatives had been reported as anxiolytic agents. Flavonoids present in this extract were correlated with flavonoids reported as anxiolytics.

  7. Chemical composition of hydroethanolic extracts from Siparuna guianensis, medicinal plant used as anxiolytics in Amazon region

    Directory of Open Access Journals (Sweden)

    Giuseppina Negri

    2012-03-01

    Full Text Available Siparuna guianensis Aubl., Siparunaceae, is used as anxiolytic plants in folk medicine by South-American indians, "caboclos" and river-dwellers. This work focused the evaluation of phenolic composition of hydroethanolic extract of S. guianensis through HPLC-DAD-ESI/MS/MS. The constituents exhibited protonated, deprotonated and sodiated molecules and the MS/MS fragmentation of protonated, deprotonated and sodiated molecules provided product ions with rich structural information. Vicenin-2 (apigenin-6,8-di-C-glucoside was the main constituent found in S. guianensis together quercetin-3,7-di-O-rhamnoside and kaempferol-3,7di-O-rhamnoside. A commercial extract of Passiflora incarnata (Phytomedicine was used as surrogate standard and also was analyzed through HPLC-DAD-ESI/ MS/MS, showing flavones C-glycosides as constituents, among them, vicenin-2 and vitexin. The main constituent was vitexin. Flavonols triglycosides was also found in low content in S. guianensis and were tentatively characterized as quercetin-3O-rutinoside-7-O-rhamnoside, quercetin-3-O-pentosyl-pentoside-7-O-rhamnoside and kaempferol-3-O-pentosyl-pentoside-7-O-rhamnoside. Apigenin and kaempferol derivatives had been reported as anxiolytic agents. Flavonoids present in this extract were correlated with flavonoids reported as anxiolytics.

  8. Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online Health Communities: A Text Mining Approach.

    Science.gov (United States)

    Abbe, Adeline; Falissard, Bruno

    2017-10-23

    Internet is a particularly dynamic way to quickly capture the perceptions of a population in real time. Complementary to traditional face-to-face communication, online social networks help patients to improve self-esteem and self-help. The aim of this study was to use text mining on material from an online forum exploring patients' concerns about treatment (antidepressants and anxiolytics). Concerns about treatment were collected from discussion titles in patients' online community related to antidepressants and anxiolytics. To examine the content of these titles automatically, we used text mining methods, such as word frequency in a document-term matrix and co-occurrence of words using a network analysis. It was thus possible to identify topics discussed on the forum. The forum included 2415 discussions on antidepressants and anxiolytics over a period of 3 years. After a preprocessing step, the text mining algorithm identified the 99 most frequently occurring words in titles, among which were escitalopram, withdrawal, antidepressant, venlafaxine, paroxetine, and effect. Patients' concerns were related to antidepressant withdrawal, the need to share experience about symptoms, effects, and questions on weight gain with some drugs. Patients' expression on the Internet is a potential additional resource in addressing patients' concerns about treatment. Patient profiles are close to that of patients treated in psychiatry. ©Adeline Abbe, Bruno Falissard. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.10.2017.

  9. Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

    Directory of Open Access Journals (Sweden)

    Debatin Thaize

    2006-01-01

    Full Text Available OBJETIVE: It has been shown that neurosteroids can either block or stimulate the development of chronic and rapid tolerance to the incoordination and hypothermia caused by ethanol consumption. The aim of the present study was to investigate the influence of isopregnanolone on the development of rapid tolerance to the anxiolytic effect of ethanol in mice. METHOD: Male Swiss mice were pretreated with isopregnanolone (0.05, 0.10 or 0.20 mg/kg 30 min before administration of ethanol (1.5 g/kg. Twenty-four hours later, all animals we tested using the plus-maze apparatus. The first experiment defined the doses of ethanol that did or did not induce rapid tolerance to the anxiolytic effect of ethanol. In the second, the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20 mg/kg on rapid tolerance to ethanol (1.5 g/kg was studied. CONCLUSIONS: The results show that pretreatment with isopregnanolone interfered with the development of rapid tolerance to the anxiolytic effect of ethanol.

  10. Comparison of Antiemetic Effects of Ondansetron Granisetron and Tropisetron For Acute Emesis In Ovarian Cancer Patients Receiving Chemotherapy With Paclitaxel and Carboplatin

    Directory of Open Access Journals (Sweden)

    Taner Turan

    2007-08-01

    CONCLUSION: Even though this study was retrospective, the treatment and patient groups were homogeneous. Both the discovery of an antiemetic that is much more effective and a protocol that is improved are essential. An emerging need for prospective studies achieved with homogeneous patient groups does exist.

  11. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial.

    Science.gov (United States)

    April, Michael D; Oliver, Joshua J; Davis, William T; Ong, David; Simon, Erica M; Ng, Patrick C; Hunter, Curtis J

    2018-02-17

    We compare aromatherapy with inhaled isopropyl alcohol versus oral ondansetron for treating nausea among emergency department (ED) patients not requiring immediate intravenous access. In a randomized, blinded, placebo-controlled trial, we enrolled a convenience sample of adults presenting to an urban tertiary care ED with chief complaints including nausea or vomiting. We randomized subjects to 1 of 3 arms: inhaled isopropyl alcohol and 4 mg oral ondansetron, inhaled isopropyl alcohol and oral placebo, and inhaled saline solution placebo and 4 mg oral ondansetron. The primary outcome was mean nausea reduction measured by a 0- to 100-mm visual analog scale from enrollment to 30 minutes postintervention. Secondary outcomes included receipt of rescue antiemetic medications and adverse events. We enrolled 122 subjects, of whom 120 (98.3%) completed the study. Of randomized subjects, 40 received inhaled isopropyl alcohol and oral ondansetron, 41 received inhaled isopropyl alcohol and oral placebo, and 41 received inhaled saline solution placebo and oral ondansetron. The mean decrease in nausea visual analog scale score in each arm was 30 mm (95% confidence interval [CI] 22 to 37 mm), 32 mm (95% CI 25 to 39 mm), and 9 mm (95% CI 5 to 14 mm), respectively. The proportions of subjects who received rescue antiemetic therapy in each arm were 27.5% (95% CI 14.6% to 43.9%), 25.0% (95% CI 12.7% to 41.2%), and 45.0% (95% CI 29.3% to 61.5%), respectively. There were no adverse events. Among ED patients with acute nausea and not requiring immediate intravenous access, aromatherapy with or without oral ondansetron provides greater nausea relief than oral ondansetron alone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  12. Association between bystander cardiopulmonary resuscitation and redeemed prescriptions for antidepressants and anxiolytics in out-of-hospital cardiac arrest survivors.

    Science.gov (United States)

    Bundgaard, Kristian; Hansen, Steen M; Mortensen, Rikke Nørmark; Wissenberg, Mads; Hansen, Malta; Lippert, Freddy; Gislason, Gunnar; Køber, Lars; Nielsen, Jimmi; Torp-Pedersen, Christian; Rasmussen, Bodil Steen; Kragholm, Kristian

    2017-06-01

    This study aimed to examine rates of redeemed prescriptions of antidepressants and anxiolytics, used as markers for cerebral dysfunction in out-of-hospital cardiac arrest (OHCA) survivors, and examine the association between bystander CPR and these psychoactive drugs. We included all 30-day survivors of OHCA in Denmark between 2001 and 2011, who had not redeemed prescriptions for antidepressants or anxiolytics in the last six months prior to OHCA. Main outcome measures were redeemed prescriptions of antidepressants and anxiolytics within one year after OHCA. Among 2,001 30-day survivors, 174 (8.6% died and 12.0% redeemed a first prescription for an antidepressant and 8.2% for an anxiolytic drug within one year after arrest. The corresponding frequencies for redeemed prescribed drugs among age- and sex-matched population controls were 7.5% and 5.2%, respectively. Among survivors who received bystander CPR, prescriptions for antidepressants and anxiolytics were redeemed in 11.1% [95% CI 9.2-13.3%] and 6.3% [95% CI 4.9-8.0%] of the cases, respectively, versus 17.2% [95% CI 13.9-21.1%] and 13.4% [95% CI 10.5-17.0%], respectively, among patients who had not received bystander CPR. Adjusted for age, sex, year of arrest, comorbidity, witnessed status and socioeconomic status, bystander CPR was associated with significant reductions in redeemed prescriptions for antidepressants, Hazard Ratio (HR) 0.71 [95% CI 0.52-0.98], P=0.031; and anxiolytics, HR 0.55 [95% CI 0.38-0.81], P=0.002. Relative to no bystander CPR, redeemed prescriptions for antidepressants and anxiolytics were significantly lower among 30-day survivors of OHCA who received bystander CPR, suggesting a cerebral dysfunction-lowering potential of bystander CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Study on interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part III. In vitro study on the adsorption of selected prokinetic drugs on sucralfate.

    Science.gov (United States)

    Grimling, Bozena; Pluta, Janusz

    2005-01-01

    Adsorbance of certain prokinetic drugs, regulating the motility of the digestive tract, on a cytoprotective drug--sucralfate was investigated. The evaluation of adsorbance capability was carried out by means of a statistical method in in vitro conditions, taking into account environmental pH, concentration of the investigated drugs as well as the form of sucralfate. Obtained results prove that the analyzed active agents are adsorbed on sucralfate at all the investigated pH ranges and the capability of sucralfate binding depends on its form and environmental pH. The highest binding capability was revealed by samples with pH = 3.6 in the presence of sucralfate in the form of suspension, while the lowest binding capability was observed at pH = 1.5 in the presence of sucralfate in the form of paste. The adsorbance capacity of sucralfate (k) at pH = 3.6 is the highest for cisaprid (k = 8.5) and it is significantly lower for metoclopramide (k = 1.5)

  14. Evaluation of anxiolytic potency of essential oil and S-(+-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice

    Directory of Open Access Journals (Sweden)

    Bing-Ho Cheng

    2015-01-01

    Full Text Available Cinnamomum osmophloeum ct. linalool (土肉桂 tǔ ròu guì is one chemotype of the indigenous cinnamons in Taiwan. This study examined the anxiolytic potency of leaf essential oil (LEO from C. osmophloeum ct. linalool and its main constituent on 4-week ICR mice using an open field test (OFT, a light–dark test (LDT and an elevated plus maze test (EPT. After oral administration of corn oil, LEO (250 mg/kg and 500 mg/kg, S-(+-linalool (500 mg/kg, R-(−-linalool (500 mg/kg, and trazodone hydrochloride (75 mg/kg for 14 days, the anxiolytic effects on mice behavior were evaluated. The results showed that LEO from C. osmophloeum ct. linalool leaves and S-(+-linalool can significantly increase the time mice remained in the center area of the OFT, the illuminated area of the LDT and the open arms of the EPT without any side effects affecting motor activity, indicating excellent anxiolytic responses. Furthermore, results from the measurements of monoamines in mice brain revealed decreases in serotonin, dopamine, and norepinephrine, which are consistent with their anxiolytic effects in animal models. The findings obtained suggest that LEO from C. osmophloeum ct. linalool and its major compound, S-(+-linalool, possess anxiolytic properties without any side effects and thus support their potential use in treatment of anxiety disorders.

  15. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.

    Science.gov (United States)

    Bercik, P; Park, A J; Sinclair, D; Khoshdel, A; Lu, J; Huang, X; Deng, Y; Blennerhassett, P A; Fahnestock, M; Moine, D; Berger, B; Huizinga, J D; Kunze, W; McLean, P G; Bergonzelli, G E; Collins, S M; Verdu, E F

    2011-12-01

    The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system. © 2011 Blackwell Publishing Ltd.

  16. Anxiolytic and antidepressive effects of magnesium in rats and their effect on general behavioural parameters

    Directory of Open Access Journals (Sweden)

    Samardžić Janko

    2011-01-01

    Full Text Available Magnesium (Mg is an essential element that catalyses more than 300 enzyme systems. Its effects on the central nervous system are exhibited through the blocking of activity of N-methyl D-aspartat (NMDA receptors and potentiating of GABA-ergic neurotransmission. Due to the vast importance of these two neurotransmission systems in the fine regulation of the central integrative function activity, the aim of this research was to test the anxiolytic and antidepressive effects of magnesium, after acute and repeated application, and its influence on general behavioural parameters. In this research Wistar albino rats were treated with increasing doses of Mg chloride 6-hydrate (MgCl 10, 20, 30 mg/kg. In order to determine anxiolytic and antidepressive properties of magnesium two models were used: elevated plus maze (EPM and forced swim test (FST. Behavioural parameters (stillness and mobility were recorded during acute and repeated administration of the active substance. Results of EPM testing showed no significant difference between groups, p>0.05. After acute application of increasing doses of magnesium chloride hydrate in FST, we showed the statistically significant difference in immobility time between the group of animals treated with Mg and the control group treated with the solvent, p<0.01. The statistically significant difference between groups treated with the lowest and the middle dose of magnesium and the controls was observed already on the first day of examining behavioural parameters (p=0.020, p=0.010. Our research has showed that magnesium, following acute administration, increases locomotor activity, and has an antidepressive but not an anxiolytic effect.

  17. Anxiolytic action of neuromedin-U and neurotransmitters involved in mice.

    Science.gov (United States)

    Telegdy, G; Adamik, A

    2013-09-10

    Peptide Neuromedin-U (NmU) is widely distributed in the central nervous system and the peripheral tissues. Its physiological effects include the regulation of blood pressure, heart rate, and body temperature, and the inhibition of gastric acid secretion. The action of NmU in rats is mediated by two G-protein-coupled receptors, NmU-1R and NmU-2R. NmU-2R is present mainly in the brain, and NmU-1R mainly in the periphery. Despite the great variety of the physiological action of NmU, little is known about its possible effects in different forms of behavior, such as anxiety. In the present work, NmU-23 (the rodent form of the peptide) was tested for its effect on anxiety in elevated plus maze test in mice. For detection of the possible involvement of neurotransmitters, the mice were pretreated with receptor blockers: haloperidol (a D2, dopamine receptor antagonist), propranolol (a β-adrenergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), phenoxybenzamine (a nonselective α-adrenergic receptor antagonist) or nitro-l-arginine (a nitric oxide synthase inhibitor). The peptide and nitro-l-arginine were administered into the lateral brain ventricle, while the receptor blockers were applied intraperitoneally. An NmU-23 dose 0.5μg elicited anxiolytic action, whereas this action is faded away when the dose was increased. For further testing therefore 0.5μg i.c.v. was used. Propranolol and atropine fully blocked the NmU-induced anxiolytic action, while haloperidol, phenoxybenzamine and nitro-l-arginine were ineffective. The results suggest that β-adrenergic and cholinergic mechanisms are involved in the anxiolytic action of NmU. © 2013.

  18. Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats.

    Science.gov (United States)

    Haller, J; Barna, I; Barsvari, B; Gyimesi Pelczer, K; Yasar, S; Panlilio, L V; Goldberg, S

    2009-07-01

    Since the discovery of endogenous cannabinoid signaling, the number of studies exploring its role in health and disease has increased exponentially. Fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of the endocannabinoid anandamide, has emerged as a promising target for anxiety-related disorders. FAAH inhibitors (e.g., URB597) increase brain levels of anandamide and induce anxiolytic-like effects in rodents. Recent findings, however, questioned the efficacy of URB597 as an anxiolytic. We tested here the hypothesis that conflicting findings are due to variations in the stressfulness of experimental conditions employed in various studies. We found that URB597 (0.1-0.3 mg/kg) did not produce anxiolytic effects when the aversiveness of testing procedures was minimized by handling rats daily before experimentation, by habituating them to the experimental room, or by employing low illumination during testing. In contrast, URB597 had robust anxiolytic effects when the aversiveness of the testing environment was increased by eliminating habituation to the experimental room or by employing bright lighting conditions. Unlike URB597, the benzodiazepine chlordiazepoxide (5 mg/kg) had anxiolytic effects under all testing conditions. The anxiolytic effects of URB597 were abolished by the cannabinoid CB1-receptor antagonist AM251, showing that they were mediated by CB1 receptors. Close inspection of experimental conditions employed in earlier reports suggests that conflicting findings with URB597 can be explained by different testing conditions, such as those manipulated in the present study. Our findings show that FAAH inhibition does not affect anxiety under mildly stressful circumstances but protects against the anxiogenic effects of aversive stimuli.

  19. COMPARISON OF ANTIEMETIC EFFICACY OF ONDANSETRON, GRANISETRON AND PALONOSETRON IN HIGH-RISK PATIENTS UNDERGOING ABDOMINAL HYSTERECTOMY UNDER GENERAL ANAESTHESIA

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2016-03-01

    Full Text Available BACKGROUND Postoperative nausea and vomiting is (PONV a very distressing complication and preventive measures are justified when the risk of PONV is very high. Ondansetron is the first 5-HT3 antagonist used alone or in combination for prophylaxis of PONV due to its lower cost. Granisetron and palonosetron are recently introduced 5-HT3 antagonists with greater affinity for 5-HT3 receptor and having longer half-life. Aim of the present study is to compare the antiemetic efficacy of ondansetron, granisetron and palonosetron in high-risk patients undergoing abdominal hysterectomy under general anaesthesia. METHODS After obtaining Institutional Ethical Committee approval and written informed consent from all the participants, 150 patients of ASA grade I & II, aged between 20-50 years and weight between 30-60 kg undergoing abdominal hysterectomy under general anaesthesia were assigned randomly in to three groups of 50 patients each using random number table receiving either ondansetron 4 mg (Group O or granisetron 2 mg (Group G or palonosetron 0.75 mg (Group P intravenously just before the induction of anaesthesia. Incidence and severity of nausea and frequency of retching and vomiting were recorded in each group at the end of 2-hour and then at 24-hour and 48-hour intervals. RESULTS The incidence of nausea during first two hours postoperatively was found to be 14(28% in Group O, which was found to be significantly higher than 6(12% in group G and 4(8% in group P (p value = 0.016. The incidence of vomiting was found to be 6(12% in group O, which was found to be significantly higher than 2(4% in both group G and group P (p value = 0.018. Number of complete responders was significantly higher in Group P and group G as compared to group O. Number of patients requiring rescue antiemetic treatment was significantly high in group O{10(20%} as compared to 3(6% in both the group G and group P. CONCLUSIONS Newly introduced 5-HT3 antagonists, granisetron and

  20. Cost-effectiveness analysis of granisetron-based versus standard antiemetic regimens in low-emetogenic chemotherapy: a hospital-based perspective from Malaysia.

    Science.gov (United States)

    Keat, Chan Huan; Ghani, Norazila Abdul

    2013-01-01

    In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

  1. 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.

  2. Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice.

    Science.gov (United States)

    Li, Wen-Jing; Yu, Hui; Yang, Jian-Min; Gao, Jing; Jiang, Hong; Feng, Min; Zhao, Yu-Xia; Chen, Zhe-Yu

    2010-08-06

    Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant. Copyright 2010 Elsevier B.V. All rights reserved.

  3. 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.

  4. Evaluation of Anxiolytic-Like Effect of Aqueous Extract of Asparagus Stem in Mice

    Science.gov (United States)

    Cheng, Long; Pan, Guo-feng; Sun, Xiao-bo; Huang, Yun-xiang; Peng, You-shun; Zhou, Lin-yan

    2013-01-01

    There are few studies on the neuropharmacological properties of asparagus, which was applied in Chinese traditional medicine as a tonic and heat-clearing agent. The present study was designed to investigate the anxiolytic-like activity of the aqueous extract of asparagus stem (AEAS) using elevated plus maze (EPM) and Vogel conflict tests (VCT) in mice. AEAS significantly increased the percentage of time spent in open arms in EPM, when compared with control group. In the Vogel conflict drinking test, the numbers of punished licks increased to 177% and 174% by the treatment of AEAS at the doses of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight), compared with control group. The serum cortisol level decreased significantly, at the same time. In conclusion, these findings indicated that the aqueous extract of asparagus stem exhibited a strong anxiolytic-like effect at dose of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight) in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder. PMID:24348707

  5. Evaluation of Anxiolytic-Like Effect of Aqueous Extract of Asparagus Stem in Mice

    Directory of Open Access Journals (Sweden)

    Long Cheng

    2013-01-01

    Full Text Available There are few studies on the neuropharmacological properties of asparagus, which was applied in Chinese traditional medicine as a tonic and heat-clearing agent. The present study was designed to investigate the anxiolytic-like activity of the aqueous extract of asparagus stem (AEAS using elevated plus maze (EPM and Vogel conflict tests (VCT in mice. AEAS significantly increased the percentage of time spent in open arms in EPM, when compared with control group. In the Vogel conflict drinking test, the numbers of punished licks increased to 177% and 174% by the treatment of AEAS at the doses of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight, compared with control group. The serum cortisol level decreased significantly, at the same time. In conclusion, these findings indicated that the aqueous extract of asparagus stem exhibited a strong anxiolytic-like effect at dose of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.

  6. Anxiolytic effects of lavender oil inhalation on open-field behaviour in rats.

    Science.gov (United States)

    Shaw, D; Annett, J M; Doherty, B; Leslie, J C

    2007-09-01

    To establish a valid animal model of the effects of olfactory stimuli on anxiety, a series of experiments was conducted using rats in an open-field test. Throughout, effects of lavender oil were compared with the effects of chlordiazepoxide (CDP), as a reference anxiolytic with well-known effects on open-field behaviour. Rats were exposed to lavender oil (0.1-1.0 ml) for 30 min (Experiment 1) or 1h (Experiment 2) prior to open-field test and in the open field or injected with CDP (10 mg/kg i.p.). CDP had predicted effects on behaviour, and the higher doses of lavender oil had some effects on behaviour similar to those of CDP. In Experiment 3, various combinations of pre-exposure times and amounts of lavender oil were used. With sufficient exposure time and quantity of lavender the same effects were obtained as in Experiment 2. Experiment 4 demonstrated that these behavioural effects of lavender could be obtained following pre-exposure, even if no oil was present in the open-field test. In Experiments 2-4, lavender oil increased immobility. Together, these experiments suggest that lavender oil does have anxiolytic effects in the open field, but that a sedative effect can also occur at the highest doses.

  7. 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.

  8. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.

    Science.gov (United States)

    Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-03-01

    To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  9. Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

    Science.gov (United States)

    Vogt, M A; Mallien, A S; Pfeiffer, N; Inta, I; Gass, P; Inta, D

    2016-03-15

    Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

    Directory of Open Access Journals (Sweden)

    Rafael G. dos Santos

    2016-03-01

    Full Text Available Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline. Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  11. A randomized controlled non-inferiority study comparing the antiemetic effect between intravenous granisetron and oral azasetron based on estimated 5-HT3 receptor occupancy.

    Science.gov (United States)

    Endo, Junki; Iihara, Hirotoshi; Yamada, Maya; Yanase, Koumei; Kamiya, Fumihiko; Ito, Fumitaka; Funaguchi, Norihiko; Ohno, Yasushi; Minatoguchi, Shinya; Itoh, Yoshinori

    2012-09-01

    The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory. Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer. Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%). Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.

  12. Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug

    Directory of Open Access Journals (Sweden)

    T Singhal

    2015-01-01

    Full Text Available Background: In the end of 2009, a large number of patients with cancer undergoing chemotherapy at the day care unit of a private hospital in Mumbai, India developed Burkholderia cepacia complex (BCC blood stream infection (BSI. Objective: The objectives were to identify the source of the outbreak and terminate the outbreak as rapidly as possible. Materials and Methods: All infection control protocols and processes were reviewed. Intensive training was started for all nursing staff involved in patient care. Cultures were sent from the environment (surfaces, water, air, intravenous fluids, disinfectants and antiseptics and opened/unopened medication. Results: A total of 13 patients with cancer with tunneled catheters were affected with BCC BSI. The isolates were of similar antimicrobial sensitivity. No significant breach of infection control protocols could be identified. Cultures from the prepared intravenous medication bags grew BCC. Subsequently, culture from unused vials of the antiemetic granisetron grew BCC, whereas those from the unopened IV fluid bag and chemotherapy medication were negative. On review, it was discovered that the outbreak started when a new brand of granisetron was introduced. The result was communicated to the manufacturer and the brand was withdrawn. There were no further cases. Conclusions: This outbreak was thus linked to intrinsic contamination of medication vials. We acknowledge a delay in identifying the source as we were concentrating more on human errors in medication preparation and less on intrinsic contamination. We recommend that in an event of an outbreak, unopened vials be cultured at the outset.

  13. A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

    Science.gov (United States)

    Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

    1992-02-01

    Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

  14. Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting.

    Science.gov (United States)

    Schwartzberg, Lee; Jackson, James; Jain, Gagan; Balu, Sanjeev; Buchner, Deborah

    2011-08-01

    It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT(3) RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied. To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT(3) RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT(3) RA cohort) among single-day HEC cycles. Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2-5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models. A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT(3) RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT(3) RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73-0.94; p = 0.0042). Results in the breast cancer and multiple cancer

  15. Acid sensing ion channel (ASIC) inhibitors exhibit anxiolytic-like activity in preclinical pharmacological models.

    Science.gov (United States)

    Dwyer, Jason M; Rizzo, Stacey J Sukoff; Neal, Sarah J; Lin, Qian; Jow, Flora; Arias, Robert L; Rosenzweig-Lipson, Sharon; Dunlop, John; Beyer, Chad E

    2009-03-01

    Acid sensing ion channels (ASICs) are proton-gated ion channels located in the central and peripheral nervous systems. Of particular interest is ASIC1a, which is located in areas associated with fear and anxiety behaviors. Recent reports suggest a role for ASIC1a in preclinical models of fear conditioning and anxiety. The present experiments evaluated various ASIC inhibitors in preclinical models of autonomic and behavioral parameters of anxiety. In addition, neurochemical studies evaluated the effects of an ASIC inhibitor (A-317567) on neurotransmitter levels in the amygdala. In electrophysiological studies using hippocampal primary neuronal cultures, three ASIC inhibitors (PcTX-1, A-317567, and amiloride) produced concentration-dependent inhibition of acid-evoked currents. In the stress-induced hyperthermia model, acute administration of psalmotoxin 1 (PcTX-1; 10-56 ng, i.c.v.), A-317567 (0.1-1.0 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) prevented stress-induced elevations in core body temperature. In the four-plate test, acute treatment with PcTX-1 (10-56 ng, i.c.v.) and A-317567 (0.01-0.1 mg/kg, i.p.), but not amiloride (3-100 mg/kg, i.p.), produced dose-dependent and significant increases in the number of punished crossings relative to vehicle-treated animals. Additionally, PcTX-1 (56-178 ng, i.c.v.), A-317567 (0.1-10 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) lacked significant anxiolytic-like activity in the elevated zero maze. In neurochemical studies, an infusion of A-317567 (100 microM) into the amygdala significantly elevated the extracellular levels of GABA, but not glutamate, in this brain region. These findings demonstrate that ASIC inhibition produces anxiolytic-like effects in some behavioral models and indicate a potential role for GABAergic mechanisms to underlie these anxiolytic-like effects.

  16. Experimental ComparativeStudy of potential anxiolytic effect of Vitamin C and Buspirone in rats

    Directory of Open Access Journals (Sweden)

    Ghada Farouk Soliman

    2018-02-01

    Full Text Available Background: Anxiety disorders are the most common of all mental health problems. They are more prevalent among women than among men, and they affect children as well as adults. The aim of the current study is to evaluate this problem via an experimental animal model and try to explore its possible mechanisms by studying the effect of Vitamin C compared to Buspirone on anxiety in rats induced by Monosodium Glutamate (MSG. Materials and Methods: 56 healthy adult male albino rats (Sprague-Dawley weighing 200-250 gm were used and divided into 7 groups (8 rats each. The first and the second groups were provided with normal saline and MSG at a dose of (2 mg/g p.o. respectively. The other five groups were given MSG and treated daily in the following way: The third and fourth groups were treated with Vitamin C (100, 200 mg/kg p.o respectively. The fifth group was treated with only Buspirone (10 mg/kg p.o., while the last sixth and seventh groups were given a combination of Buspirone and Vitamin C with (100, 200 mg/kg respectively. After 3 weeks, the open field and successive alleys tests were used to assess behavioral changes. The percentage change of systolic blood pressure (SBP was measured. Additionally, glutathione reductase (GR, malondialdehyde (MDA, and corticosterone levels were determined biochemically. Results: The results after 3 weeks revealed that MSG group showed significant anxiogenic effects in both behavioral tests, with an increased percentage change of SBP in addition to increased malondialdehyde and corticosterone level measured statistically. While the results of the treated groups revealed that the Vitamin C (100mg/kg treated group demonstrated significant improvement in anxiety levels in the open field test, there were no significant changes in the biochemical assessment. However, vitamin C (200mg/kg treated group revealed a significant anxiolytic effect in behavioral tests, improved glutathione and malondialdehyde with low

  17. 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)

  18. Sedative and Anxiolytic-Like Actions of Ethanol Extract of Leaves of Glinus oppositifolius (Linn. Aug. DC.

    Directory of Open Access Journals (Sweden)

    Md. Moniruzzaman

    2016-01-01

    Full Text Available Glinus oppositifolius is a small herb, widely used in the traditional medicine of Bangladesh in treatment of a variety of diseases and disorders such as insomnia, pain, inflammation, jaundice, and fever. The present study evaluated the sedative and anxiolytic potentials of the ethanol extract of leaves of G. oppositifolius (EEGO in different behavioral models in mice. The sedative activity of EEGO was investigated using hole cross, open field, rotarod, and thiopental sodium- (TS- induced sleeping time determination tests, where the elevated plus maze (EPM and light-dark box (LDB exploration tests were employed to justify the anxiolytic potentials in mice at the doses of 50, 100, and 200 mg/kg. The results demonstrated that EEGO significantly inhibited the exploratory behavior of the animals both in hole cross and in open field tests in a dose-dependent manner. It also decreased motor coordination and modified TS-mediated hypnosis in mice. In addition, EEGO showed anxiolytic potential by increasing the number and time of entries in the open arm of EPM, which is further strengthened by increase in total time spent in the light part of LDB. Therefore, this study suggests the sedative and anxiolytic properties of the leaves of G. oppositifolius and supports the traditional use of this plant in treatment of different psychiatric disorders including insomnia.

  19. Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT₁A and 5-HT₇ Antagonists in Animal Models.

    Directory of Open Access Journals (Sweden)

    Karolina Pytka

    Full Text Available The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxyethoxy]ethyl}-4-(2-methoxyphenylpiperazynine hydrochloride (HBK-14 and 2-[2-(2-chloro-6-methylphenoxyethoxy]ethyl-4-(2- methoxyphenylpiperazynine dihydrochloride (HBK-15 in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic α1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14-FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg and (HBK-15-FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg. We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds.

  20. Preclinical evidence of the anxiolytic and sedative-like activities of Tagetes erecta L. reinforces its ethnobotanical approach.

    Science.gov (United States)

    Pérez-Ortega, Gimena; Angeles-López, Guadalupe Esther; Argueta-Villamar, Arturo; González-Trujano, María Eva

    2017-09-01

    Morelos State is one of the regions of Mexico where several plant species are used in traditional medicine. Species from Tagetes genus (Asteraceae) are reported as useful in infusion to treat stomachache and intestinal diseases, but also as tranquilizers. In this study, medicinal uses of T. erecta including its depressant effect on the central nervous system (CNS) were explored by interviewing healers and merchants of local markets of Morelos State, and by investigation of the phytochemical and pharmacological tranquilizing properties. Specific anxiolytic and/or sedative-like responses of different doses of T. erecta (10, 30 and 100 or 300mg/kg, i.p.) were investigated using experimental models in mice such as: open-field, exploration cylinder, hole-board, and the barbituric-induced hypnosis potentiation. The possible anxiolytic mechanism of action was assessed in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.), antagonists of 5-HT 1A and GABA/BDZs receptors, respectively. Individual flavonoids reported in this species were also evaluated in these experimental models. As a result of this study, healers and merchants from ten local regions of Morelos State recommended T. erecta flowers as an infusion or as a tincture for several culture-bound syndromes associated with CNS, among others. Anxiolytic and sedative-like activities of the T. erecta aqueous and organic polar extracts were corroborated in these models associated to a participation of rutin, kaempferol, quercetin, kaempferitrin, and β-sitosterol constituents; where 5-HT 1A , but not BDZs, receptors were involved as anxiolytic mechanism of action. These data support the anxiolytic and sedative-like properties of T. erecta in traditional medicine by involving mainly serotonergic neurotransmission because of the presence in part of flavonoids and the terpenoid β-sitosterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Directory of Open Access Journals (Sweden)

    Aviva Breuer

    Full Text Available Cannabidiol (CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101 (1, is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  2. Differential role of AMPA receptors in mouse tests of antidepressant and anxiolytic action

    DEFF Research Database (Denmark)

    Andreasen, Jesper T; Fitzpatrick, Ciaran M; Larsen, Maria

    2015-01-01

    and memory we also tested if GYKI-53655 disrupted performance in the V-maze test for attention-dependent behaviour, and the social transmission of food preference (STFP) test of long-term memory. LY451646 (3 mg/kg) showed an antidepressant-like profile in the FST and TST, and GYKI-53655 (≥ 5 mg/kg) had......-like effect in the FST (≥ 10 mg/kg), but not TST, an anxiolytic-like effect in the EZM (≥ 3 mg/kg) and MB test (≥ 2.5 mg/kg), and an anxiogenic-like effect in the NIH test (≥ 30 mg/kg). GYKI-53655 did not affect cognitive performance in the V-maze or STFP tests. Collectively, these findings suggest...

  3. Chemical composition and anxiolytic-like effects of the Bauhinia platypetala

    Directory of Open Access Journals (Sweden)

    Francisco José Borges dos Santos

    2012-01-01

    Full Text Available The pantropical genus Bauhinia, Fabaceae, known popularly as cow's foot, is widely used in folk medicine as antidiabetic. Behavioral effects of the ethanolic extract and ethereal, aqueous and ethyl acetate fractions from B. platypetala Benth. ex Hemsl. leaves were studied in male Swiss mice. The ethanolic extract and fractions were administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior were monitored. Anxiolytic-like properties were studied in the elevated plus-maze test and the possible antidepressant-like actions were evaluated in the forced swimming test. The results revealed that only the highest dose of the ethereal fraction (50 mg/kg, i.p. caused a significant decrease in total motility, locomotion and rearing. Sole dose injected (50 mg/kg of ethanolic extract and ethereal fractions increased the exploration of the elevated plus-maze open arms in a similar way to that of diazepam (2 mg/kg, i.p.. In the forced swimming test, the ethanolic extract and their fractions (12.5, 25 or 50 mg/kg was not as effective as paroxetine (10 or 20 mg/kg, i.p. and imipramine (25 or 50 mg/kg, i.p. in reducing immobility. These results suggest that some of the components of the ethanolic extract and of the ethereal fraction from B. platypetala, such as p-cymene, phytol, D-lactic acid, hexadecanoic acid, among others, may have anxiolytic-like properties, which deserve further investigation. Furthermore, the results obtained indicate that ethanolic extract from B. platypetala and their fractions do not present antidepressive properties. However, these properties cannot be related to the chemical constituents identified in this specie.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Primary care hypnotic and anxiolytic prescription: Reviewing prescribing practice over 8 years

    Directory of Open Access Journals (Sweden)

    Lloyd D Hughes

    2016-01-01

    Full Text Available Introduction: Over the last few years, hypnotic and anxiolytic medications have had their clinical efficacy questioned in the context of concerns regarding dependence, tolerance alongside other adverse effects. It remains unclear how these concerns have impacted clinical prescribing practice. Materials and Methods: This is a study reviewing community-dispensed prescribing data for patients on the East Practice Medical Center list in Arbroath, Scotland, in 2007, 2011 and 2015. Anxiolytic and hypnotic medications were defined in accordance with the British National Formulary chapter 4.1.1 and chapter 4.1.2. All patients receiving a drug within this class in any of the study years were collated and anonymized using primary care prescribing data. The patients′ age, gender, name of the prescribed drug(s, and total number of prescriptions in this class over the year were extracted. Results: The proportion of patients prescribed a benzodiazepine medication decreased between 2007 and 2015: 83.8% (n = 109 in 2007, 70.5% (n = 122 in 2011, and 51.7% (n = 138 in 2015 (P = 0.006. The proportion of these patients prescribed a nonbenzodiazepine drug increased between 2007 and 2015: 30% (n = 39 in 2007, 46.2% (n = 80 in 2011, and 52.4% (n = 140 in 2015 (P = 0.001. There was a significant increase in the number of patients prescribed melatonin (P = 0.020. Discussion: This study reports a reduction in benzodiazepine prescriptions in primary care alongside increases in nonbenzodiazepine and melatonin prescribing, with an increase in prescribing rates of this drug class overall. Conclusion: Changes in this prescribing practice may reflect the medicalization of insomnia, local changes in prescribing practice and alongside national recommendations.

  6. Stressful life events and social health factors in women using anxiolytics and antidepressants: an Italian observational study in community pharmacies.

    Science.gov (United States)

    D'Incau, Paola; Barbui, Corrado; Tubini, Jacopo; Conforti, Anita

    2011-04-01

    In Italy, as in all of Europe, women differ from men in that they are somewhat more sensitive to the depressogenic effects of stressful life events related to their social networks and emotional sphere. Women are more likely than men to have experienced poverty, gender discrimination, and physical and sexual abuse. The purpose of this study was to expand the knowledge about the occurrence of stressful life events in women exposed and not exposed to anxiolytics and antidepressants in a community pharmacy setting. Women attending 100 community pharmacies in the Italian Veneto region were surveyed by pharmacists with regard to a number of general features of their current pharmacologic treatment. Women independently completed a written self-assessment questionnaire that focused on stressful life events. Unconditional logistic regression analysis was performed to investigate the association between anxiolytics and antidepressants use and potential factors, including stressful life events. The study population comprised 11,357 women. One or more stressful life events occurred in 90% of the women treated with anxiolytics and/or antidepressants (users [n = 3848]) and in 74% of the women not treated with these drugs (nonusers [n = 7509]) (odds ratio = 3.19; 95% CI, 2.83-3.60). On average, the life events occurred during the previous 6 months and the women considered the influence of these events on their well-being to be severe. After the unconditional logistic regression analysis, the association between anxiolytics and/or antidepressants use remained positive for most of the stressful life events studied as well as for other factors: separation/divorce, living alone or with others (family or friends), unemployment, whether currently being seen by a psychologist/psychiatrist, and treatment with drugs for the alimentary tract and metabolism, cardiovascular system, or nervous system. A significant association between stressful life events and anxiolytics and

  7. S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Indira Mendez-David

    2017-07-01

    Full Text Available Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT and in the Chronic Mild Stress (CMS model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM, open field (OF, splash test (ST, forced swim test (FST, tail suspension test (TST, fur coat state and novelty suppressed feeding (NSF as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.. In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p. during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model, neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg and EPM (from 1 mg/kg. In the CMS

  8. Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

    OpenAIRE

    Md. Josim Uddin; A. S. M. Ali Reza; Md. Abdullah-Al-Mamun; Mohammad S. H. Kabir; Mst. Samima Nasrin; Sharmin Akhter; Md. Saiful Islam Arman; Md. Atiar Rahman

    2018-01-01

    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...

  9. Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on behavioral activities of mice.

    Science.gov (United States)

    Harsha, Singapura Nagesh; Anilakumar, Kandangath Raghavan

    2013-01-01

    Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known for its medicinal properties. This study aimed to understand the mechanism of Lactuca sativa extract with respect to pharmacological action.We investigated the anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on mice. The behavioral tests performed on mice models to assess anti-anxiety properties were: open field test (OFT), elevated plus maze test (EPM), elevated T maze test, and marble burying test. Increased locomotor activity and time spent in the "open-arm" were observed in extract fed group. Malondialdehyde (MDA) and nitrite levels were decreased, catalase and glutathione levels were increased in Lactuca sativa treated mice. The data obtained in the present study suggests that the extract of Lactuca sativa can afford significant protection against anxiolytic activity.

  10. Anxiolytic effects of buspirone and MTEP in the Porsolt Forced Swim Test.

    Science.gov (United States)

    Lee, Kaziya M; Coelho, Michal A; Sern, Kimberly R; Class, MacKayla A; Bocz, Mark D; Szumlinski, Karen K

    2017-01-01

    Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test (FST) is employed as a predictor of antidepressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anxiety-related behaviors on various behavioral tests with reduced immobility in the FST. Further, this behavioral profile correlates with increased mGlu5 protein expression within limbic brain regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the reduced immobility exhibited by alcohol-withdrawn mice when tested in the FST might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we evaluated whether or not the decreased FST immobility during alcohol withdrawal responds to systemic treatment with a behaviorally-effective dose of the prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance of the withdrawal-induced increase in mGlu5 expression for FST behavior by comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day, multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases glutamate-related protein expression during early withdrawal. Control animals received only water. At 24hr withdrawal, animals from each drinking condition were subdivided into groups and treated with an IP injection of buspirone, MTEP, or vehicle, 30min prior to the FST. Drug effects on general locomotor activity were also assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly reduced immobility in the FST compared to water controls. Both buspirone and MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest increase also seen in water controls. No significant group differences were observed for

  11. Phytochemical screening, acute toxicity, anxiolytic and antidepressant activities of the Nelumbo nucifera fruit.

    Science.gov (United States)

    Rajput, Muhammad Ali; Khan, Rafeeq Alam

    2017-06-01

    Recently use of herbal therapies and diet rich in flavonoids and vitamin C have increased significantly to treat minor to modest anxiety disorders and various forms of depression. But further research and studies are necessary to evaluate the pharmacological & toxicological effects of plants. Hence present study was designed to conduct phytochemical screening, acute toxicity study, anxiolytic and antidepressant activities of the ethanol extract of Nelumbo nucifera fruit in order to ascertain its therapeutic potential. The qualitative phytochemical screening of the seed pods of the N. nucifera fruit extract exposed the existence of flavonoids, saponins, alkaloids, tannins and terpenoids in it. The acute toxicity of the N. nucifera fruit extract in mice revealed its LD 50 value to be greater than 5000 mg/kg. Antianxiety activity was determined by elevated plus maze and light and dark test using 35 male Wister rats weighing 200-220 g which were equally divided in to 5 groups. The animals used in EPM underwent testing in light and dark box just 30 min after EPM. The antidepressant effect was assessed by forced swimming test using 35 male albino mice weighing 20-25 g equally divided in to 5 groups. In elevated plus maze, N. nucifera fruit extract exhibited substantial rise in number of open arm entries and time spent in open arms at dose 50 mg/kg while highly noteworthy increase in both parameters were observed at extract doses 100 and 200 mg/kg as compared to control. In light dark test highly significant increase in the percentage of time spent in light compartment was observed as compared to control. In forced swimming test highly noteworthy decline in duration of immobility was recorded at doses 100 and 200 mg/kg on 15th day i-e after administration of 14 doses, as compared to control; whereas same doses demonstrated significant decrease as compared to control in duration of immobility after single dose administration i-e on 2nd day of experiment. Thus N

  12. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice.

    Science.gov (United States)

    Sena, Maria Clecia P; Nunes, Fabíola C; Salvadori, Mirian G S Stiebbe; Carvalho, Cleyton Charles D; Morais, Liana Clebia S L; Braga, Valdir A

    2011-01-01

    Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n = 9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n = 8 for each group). The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  13. Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats.

    Science.gov (United States)

    Rahmati, Batool; Kiasalari, Zahra; Roghani, Mehrdad; Khalili, Mohsen; Ansari, Fariba

    2017-12-01

    Anxiety and depression are common in Alzheimer's disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug. The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour. Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1 mg/kg) intraperitoneally (i.p.), daily and 30 min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400 mg/kg), 30 min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity. Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42 ± 2.60) (p ≤ 0.001), whereas lavender (200 and 400 mg/kg) enhanced it (83.12 ± 5.20 and 95 ± 11.08, respectively) (p ≤ 0.05). Also, lavender pretreatment in 200 and 400 mg/kg enhanced time spent on the open arms (15.4 ± 3.37 and 32.1 ± 3.46, respectively) (p ≤ 0.001). On the contrary, while immobility time was enhanced by scopolamine (296 ± 4.70), 100, 200 and 400 mg/kg lavender reduced it (193.88 ± 22.42, 73.3 ± 8.25 and 35.2 ± 4.22, respectively) in a dose-dependent manner (p ≤ 0.001). Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.

  14. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

    Directory of Open Access Journals (Sweden)

    Maria Clecia P. Sena

    2011-01-01

    Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  15. [Determining factors for the use of anxiolytic and hypnotic drugs in the elderly].

    Science.gov (United States)

    Téllez-Lapeira, Juan M; López-Torres Hidalgo, Jesús; Gálvez-Alcaraz, Luis; Párraga-Martínez, Ignacio; Boix-Gras, Clotilde; García-Ruiz, Antonio

    To estimate the prevalence of self-reported anxiety/hypnotics use in adults 65 years and older and identify potential factors that determine the use of these drugs. Cross-sectional study conducted on a study population of 1,161 non-institutionalised adults 65 years old and older with enough ability to conduct a personal interview. Participants were randomly selected from health care registers. The main outcomes of interest included consumption of anxiolytics, hypnotics and other drugs (filed by ATC classification system), mood (based on the Yesavage geriatric depression scale), cognitive status (Pfeiffer questionnaire), physical-functional assessment of basic activities of daily living (Katz index), health problems (ICPC-2 classification WONCA), and sociodemographic variables. The prevalence of self-reported anxiety/hypnotics consumption was 16.6% (95% CI: 14.5 - 18.7), of which 90.5% were benzodiazepines (BZD), mainly lorazepam (39.4% of BZD). Long half-life BZD accounted for 24.7% of BZD. Hypnotics accounted for 27.5% of anxiolytics/hypnotics. The use of sedatives/hypnotics was independently associated with other drugs (non-psychotropics) consumption (OR 6.8, 95% CI: 2.1-22.0), presence of established depression (OR: 2.5; 95% CI: 1.0 -5.9), presence of 4 or more comorbidities (OR: 2.0; 95% CI: 1.4-2.9), being female (OR 2.1, 95% CI: 1.5-3.1) and being dependent for basic activities of daily living (OR: 1.8, 95% CI: 1.1-2.9). The prevalence of sedatives/hypnotics use in the elderly from Albacete is high. Several factors were identified as potential determinants of sedatives/hypnotics use in our study population. It will be important to evaluate the misuse of these drugs in order to develop effective, efficient and safe prescription strategies. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. An in vivo evaluation of the change in the pulpal oxygen saturation after administration of preoperative anxiolytics and local anesthesia

    Directory of Open Access Journals (Sweden)

    Krishna P. Shetty

    2016-03-01

    Full Text Available Background. Given the influence of systemic blood pressure on pulpal blood flow, anxiolytics prescribed may alter the pulpal blood flow along with the local anesthetic solution containing a vasoconstrictor. This study evaluated the impact of preoperative anxiolytics and vasoconstrictors in local anesthetic agents on pulpal oxygen saturation. Methods. Thirty anxious young healthy individuals with a mean age of 24 years were randomly selected using the Corah’s Dental Anxiety Scale (DAS. After checking the vital signs the initial pulpal oxygen saturation (initial SpO2 was measured using a pulse oximeter. Oral midzolam was administered at a dose of 7.5 mg. After 30 min, the vital signs were monitored and the pulpal oxygen saturation (anxiolytic SpO2 was measured. A total of 1.5 mL of 2% lidocaine with 1:200000 epinephrine was administered as buccal infiltration anesthesia and 10 min the final pulpal oxygen saturation (L.A SpO2 was measured. Results. The mean initial (SpO2 was 96.37% which significantly decreased to 90.76% (SpO2 after the administration of the anxiolytic agent. This drop was later accentuated to 85.17% (SpO2 after administration of local anesthetic solution. Statistical significance was set at P<0.0001. Conclusion. High concentrations of irritants may permeate dentin due to a considerable decrease in the pulpal blood flow from crown or cavity preparation. Therefore, maintaining optimal blood flow during restorative procedures may prevent pulpal injury.

  17. Koumine exhibits anxiolytic properties without inducing adverse neurological effects on functional observation battery, open-field and Vogel conflict tests in rodents.

    Science.gov (United States)

    Chen, Chao-Jie; Zhong, Zhi-Feng; Xin, Zhi-Ming; Hong, Long-Hui; Su, Yan-Ping; Yu, Chang-Xi

    2017-04-01

    Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.

  18. p-Coumaric acid activates the GABA-A receptor in vitro and is orally anxiolytic in vivo.

    Science.gov (United States)

    Scheepens, Arjan; Bisson, Jean-Francois; Skinner, Margot

    2014-02-01

    The increasing prevalence and social burden of subclinical anxiety in the western world represents a significant psychosocial and financial cost. Consumers are favouring a more natural and nonpharmacological approach for alleviating the effects of everyday stress and anxiety. The gamma-aminobutyric acid (GABA) receptor is the primary mediator of central inhibitory neurotransmission, and GABA-receptor agonists are well known to convey anxiolytic effects. Using an in vitro screening approach to identify naturally occurring phytochemical GABA agonists, we discovered the plant secondary metabolite p-coumaric acid to have significant GABAergic activity, an effect that could be blocked by co-administration of the specific GABA-receptor antagonist, picrotoxin. Oral administration of p-coumaric acid to rodents induced a significant anxiolytic effect in vivo as measured using the elevated plus paradigm, in line with the effects of oral diazepam. Given that p-coumaric acid is reasonably well absorbed following oral consumption in man and is relatively nontoxic, it may be suitable for the formulation of a safe and effective anxiolytic functional food. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Evaluation of the Anxiolytic and Antidepressant Activities of the Aqueous Extract from Camellia euphlebia Merr. ex Sealy in Mice

    Directory of Open Access Journals (Sweden)

    Dongye He

    2015-01-01

    Full Text Available Camellia euphlebia Merr. ex Sealy is a traditional Chinese medicine that has been widely used for improvement of human emotions in the Guangxi Province of southern China. However, there are no studies about the anxiolytic and antidepressant activities of Camellia euphlebia. This study evaluated the anxiolytic and antidepressant activities of the aqueous extract from Camellia euphlebia (CEE in mice. We found that administration of 400 mg/kg CEE or 20 mg/kg fluoxetine for 7 days significantly reduced the immobility time in both TST and FST. Oral administration of 100 mg/kg extract or 4 mg/kg diazepam for 7 days significantly increased the percentage of time spent and the number of entries into the open arms of the EPMT. In addition, the time spent by mice in the illuminated side of the LDBT was increased. Furthermore, pretreatment with 400 mg/kg CEE for 7 days significantly elevated the level of 5-HT and DA in the whole brain of mice. These results provide support for the potential anxiolytic and antidepressant activity of Camellia euphlebia and contribute towards validation of the traditional use of Camellia euphlebia in the treatment of emotional disorders.

  20. Association between bystander cardiopulmonary resuscitation and redeemed prescriptions for antidepressants and anxiolytics in out-of-hospital cardiac arrest survivors

    DEFF Research Database (Denmark)

    Bundgaard, Kristian; Hansen, Steen M; Mortensen, Rikke Nørmark

    2017-01-01

    AIM: This study aimed to examine rates of redeemed prescriptions of antidepressants and anxiolytics, used as markers for cerebral dysfunction in out-of-hospital cardiac arrest (OHCA) survivors, and examine the association between bystander CPR and these psychoactive drugs. METHODS: We included all....... Among survivors who received bystander CPR, prescriptions for antidepressants and anxiolytics were redeemed in 11.1% [95% CI 9.2-13.3%] and 6.3% [95% CI 4.9-8.0%] of the cases, respectively, versus 17.2% [95% CI 13.9-21.1%] and 13.4% [95% CI 10.5-17.0%], respectively, among patients who had not received...... bystander CPR. Adjusted for age, sex, year of arrest, comorbidity, witnessed status and socioeconomic status, bystander CPR was associated with significant reductions in redeemed prescriptions for antidepressants, Hazard Ratio (HR) 0.71 [95% CI 0.52-0.98], P=0.031; and anxiolytics, HR 0.55 [95% CI 0...

  1. Studies into the anxiolytic actions of agomelatine in social isolation reared rats: Role of corticosterone and sex.

    Science.gov (United States)

    Regenass, Wilmie; Möller, Marisa; Harvey, Brian H

    2018-02-01

    Anxiety disorders are severely disabling, while current pharmacological treatments are complicated by delayed onset, low remission rates and side-effects. Sex is also noted to contribute towards illness severity and treatment response. Agomelatine is a melatonin (MT 1 /MT 2 ) agonist and serotonin (5-HT 2C ) antagonist purported to be anxiolytic in clinical and some pre-clinical studies. We undertook a detailed analysis of agomelatine's anxiolytic activity in a neurodevelopmental model of anxiety, the social isolation reared rat. Rats received sub-chronic treatment with vehicle or agomelatine (40 mg/kg per day intraperitoneally at 16:00 h for 16 days), with behaviour analysed in the open field test, social interaction test and elevated plus maze. The contribution of corticosterone and sex was also studied. Social isolation rearing increased locomotor activity and reduced social interaction in the social interaction test, and was anxiogenic in the elevated plus maze in males and females. Agomelatine reversed these behaviours. Male and female social isolation reared rats developed anxiety-like behaviours to a similar degree, although response to agomelatine was superior in male rats. Social isolation rearing decreased plasma corticosterone in both sexes and tended to higher levels in females, although agomelatine did not affect corticosterone in either sex. Concluding, agomelatine is anxiolytic in SIR rats, although correcting altered corticosterone could not be implicated. Sex-related differences in the response to agomelatine are evident.

  2. Anxiolytic-Like Effect of a Salmon Phospholipopeptidic Complex Composed of Polyunsaturated Fatty Acids and Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Nabila Belhaj

    2013-10-01

    Full Text Available A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose-dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from this natural product. The characterization of mineral composition, amino acid and fatty acids was carried out. Stability of nanoemulsions allowed us to realize a behavioral study conducted with four different tests on 80 mice. This work highlighted the dose dependent effects of the natural complex and its various fractions over a period of 14 days compared to a conventional anxiolytic. The intracellular redox status of neural cells was evaluated in order to determine the free radicals scavenging potential of these products in the central nervous system (CNS, after mice sacrifice. The complex peptidic fraction showed a strong scavenging property and similar results were found for the complex as well as its lipidic fraction. For the first time, the results of this study showed the anxiolytic-like and neuroprotective properties of a phospholipopeptidic complex extracted from salmon head. The applications on anxiety disorders might be relevant, depending on the doses, the fraction used and the chronicity of the supplementation.

  3. Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

    Science.gov (United States)

    Tanaka, Yoshihiro; Akiyoshi, Jotaro; Kawahara, Yoshinari; Ishitobi, Yoshinobu; Hatano, Koji; Hoaki, Nobuhiko; Mori, Ayumi; Goto, Shinjiro; Tsuru, Jusen; Matsushita, Hirotaka; Hanada, Hiroaki; Kodama, Kensuke; Isogawa, Koichi; Kitamura, Hirokazu; Fujikura, Yoshihisa

    2011-04-01

    Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Chronic fluoxetine treatment induces anxiolytic responses and altered social behaviors in medaka, Oryzias latipes.

    Science.gov (United States)

    Ansai, Satoshi; Hosokawa, Hiroshi; Maegawa, Shingo; Kinoshita, Masato

    2016-04-15

    Medaka (Oryzias latipes) is a small freshwater teleost that is an emerging model system for neurobehavioral research and toxicological testing. The selective serotonin reuptake inhibitor class of antidepressants such as fluoxetine is one of the widely prescribed drugs, but little is known about the effects of these drugs on medaka behaviors. To assess the behavioral effects of fluoxetine, we chronically administrated fluoxetine to medaka adult fish and analyzed the anxiety-related and social behaviors using five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and social interaction) with an automated behavioral testing system. Fish chronically treated with fluoxetine exhibited anxiolytic responses such as an overall increased time spent in the top area in the diving test and an increased time spent in center area in the open-field test. Analysis of socially evoked behavior showed that chronic fluoxetine administration decreased the number of mirror biting times in the mirror-biting test and increased latency to first contact in the social interaction test. Additionally, chronic fluoxetine administration reduced the horizontal locomotor activity in the open-field test but not the vertical activity in the diving test. These investigations are mostly consistent with previous reports in the other teleost species and rodent models. These results indicate that behavioral assessment in medaka adult fish will become useful for screening of effects of pharmaceutical and toxicological compounds in animal behaviors. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Anxiolytic-like effect of oxytocin in the simulated public speaking test.

    Science.gov (United States)

    de Oliveira, Danielle C G; Zuardi, Antonio W; Graeff, Frederico G; Queiroz, Regina H C; Crippa, José A S

    2012-04-01

    Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test. Assessments were made across time during the experimental session: (1) baseline (-30 min); (2) pre-test (-15 min); (3) anticipation of the speech (50 min); (4) during the speech (1:03 h), post-test time 1 (1:26 h), and post-test time 2 (1:46 h). Subjective states were evaluated by self-assessment scales. Cortisol serum and plasma adrenocorticotropic hormone (ACTH) were measured. Additionally, heart rate, blood pressure, skin conductance, and the number of spontaneous fluctuations in skin conductance were measured. Compared with placebo, OT reduced the Visual Analogue Mood Scale (VAMS) anxiety index during the pre-test phase only, while increasing sedation at the pre-test, anticipation, and speech phases. OT also lowered the skin conductance level at the pre-test, anticipation, speech, and post-test 2 phases. Other parameters evaluated were not significantly affected by OT. The present results show that OT reduces anticipatory anxiety, but does not affect public speaking fear, suggesting that this hormone has anxiolytic properties.

  6. Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics.

    Science.gov (United States)

    Vestergaard, Peter

    2008-09-01

    Many central nervous system active drugs can alter postural balance, increasing the risk of fractures. Anxiolytics and sedatives include the benzodiazepines, and these have been associated with a limited increase in the risk of fractures, even at low doses, probably from an increased risk of falls. No systematic differences have been shown between benzodiazepines with long and short half-lives. Although the increase in risk of fractures was limited, care must still be taken when prescribing for older fall-prone subjects at risk of osteoporosis. Neuroleptics may be associated with a decrease in bone mineral density and a very limited increase in fracture risk. Antidepressants are associated with a dose-dependent increase in the risk of fractures. The increase in relative risk of fractures seems to be larger with selective serotonin reuptake inhibitors (SSRIs) than with tricyclic antidepressants. The reason for this is not known but may be linked to serotonin effects on bone cells and the risk of falls. With the wide use of SSRIs, more research is needed. Lithium is associated with a decrease in the risk of fractures. This may be linked to its effects on the Wnt glycoprotein family, which is a specialised signalling system for certain cell types.

  7. Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

    Directory of Open Access Journals (Sweden)

    Lucia Marseglia

    2015-01-01

    Full Text Available Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.

  8. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.

    Science.gov (United States)

    Wen, D; Sun, D; Zang, G; Hao, L; Liu, X; Yu, F; Ma, C; Cong, B

    2014-09-26

    Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. The effect of BLA GABAB receptors in anxiolytic-like effect and aversive memory deficit induced by ACPA

    Directory of Open Access Journals (Sweden)

    Katayoon Kangarlu Haghighi

    2016-07-01

    Full Text Available Background: As a psychoactive plant, Cannabis sativa (Marijuana is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA GABAB receptors in arachydonilcyclopropylamide (ACPA-induced anxiolytic-like effect and aversive memory deficit in adult male mice. Methods: This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran, weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM to examine memory and anxiety behavior (test-retest protocol. ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala. Results: Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABAB receptor agonist impaired the aversive memory while phaclofen (GABAB receptor antagonist improved it. Interestingly, pretreatment with a sub

  10. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Science.gov (United States)

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated

  11. Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R-CHOP.

    Science.gov (United States)

    Uchida, Mayako; Mori, Yasuo; Nakamura, Tsutomu; Kato, Koji; Kamezaki, Kenjiro; Takenaka, Katsuto; Shiratsuchi, Motoaki; Kadoyama, Kaori; Miyamoto, Toshihiro; Akashi, Koichi

    2017-01-01

    In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.

  12. Comparison of palanosetron, granisetron and ondansetron as anti-emetics for prevention of postoperative nausea and vomiting in patients undergoing middle ear surgery.

    Science.gov (United States)

    Basu, Anjana; Saha, Debdas; Hembrom, Bani P; Roy, Amit; Naaz, Anjum

    2011-05-01

    The objective of the study was to compare the efficacy of palanosetron (0.25 mg), granisetron (3.0 mg) and ondansetron (8.0 mg) used as anti-emetics for the prevention of postoperative nausea/vomiting in patients undergoing middle ear surgery. The study was done among 75 adult patients (age group 30-45 years) of which 50 were males and rest (25) females, all of ASA I and ASA II. The patients were randomly allocated into 3 equal groups: Group I (n = 25) received injection palanosetron (0.25 mg) IV, group II (n = 25) received injection granisetron (3 mg) IV and group III (n = 25) received injection ondansetron (8.0 mg) IV at the end of the surgical procedure. A standard general anaesthesia technique was employed. Emetic episodes and safety assessments were performed during two periods of 0-6 hours in the postanaesthesia care unit and 6-24 hours in the ward after anaesthesia. The incidence of emesis-free patients during the 0-6 hours period was 100% for group I; 72% for group II and 56% for group III. During the 6-24 hours period incidence of emesis-free patients were 96% for group I; 56% for group II and 32% for group III. So to conclude, a single dose of palanosetron (0.25 mg) is a superior anti-emetic to granisetron (3.0 mg) or ondansetron (8.0 mg) in complete prevention of postoperative nausea and vomiting after middle ear surgery during the first 24 hours period.

  13. Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

    Science.gov (United States)

    Hanai, Akiko; Ishiguro, Hiroshi; Sozu, Takashi; Tsuda, Moe; Arai, Hidenori; Mitani, Akira; Tsuboyama, Tadao

    2016-01-01

    Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy.

  14. Eliminating Postoperative Nausea and Vomiting in Outpatient Surgery with Multimodal Strategies including Low Doses of Nonsedating, Off-Patent Antiemetics: Is “Zero Tolerance“ Achievable?

    Directory of Open Access Journals (Sweden)

    Susan J. Skledar

    2007-01-01

    Full Text Available For ondansetron, dexamethasone, and droperidol (when used for prophylaxis, each is estimated to reduce risk of postoperative nausea and/or vomiting (PONV by approximately 25%. Current consensus guidelines denote that patients with 0–1 risk factors still have a 10–20% risk of encountering PONV, but do not yet advocate routine prophylaxis for all patients with 10–20% risk. In ambulatory surgery, however, multimodal prophylaxis has gained favor, and our previously published experience with routine prophylaxis has yielded PONV rates below 10%. We now propose a “zero-tolerance” antiemetic algorithm for outpatients that involves routine prophylaxis by first avoiding volatile agents and opioids to the extent possible, using locoregional anesthesia, multimodal analgesia, and low doses of three nonsedating off-patent antiemetics. Routine oral administration (immediately on arrival to the ambulatory surgery suite of perphenazine 8 mg (antidopaminergic or cyclizine 50 mg (antihistamine, is followed by dexamethasone 4 mg i.v. after anesthesia induction (dexamethasone is avoided in diabetic patients. At the end of surgery, ondansetron (4 mg i.v., now off-patent is added. Rescue therapy consists of avoiding unnecessary repeat doses of drugs acting by the same mechanism: haloperidol 2 mg i.v. (antidopaminergic is prescribed for patients pretreated with cyclizine or promethazine 6.25 mg i.v. (antihistamine for patients having been pretreated with perphenazine. If available, a consultation for therapeutic acupuncture procedure is ordered. Our approach toward “zero tolerance” of PONV emphasizes liberal identification of and prophylaxis against common risks.

  15. Interest of the trajectory method for the evaluation of outcomes after in utero drug exposure: example of anxiolytics and hypnotics.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Chouquet, Cécile; Savy, Nicolas; Lacroix, Isabelle; Beau, Anna-Belle; Montastruc, Jean-Louis; Damase-Michel, Christine

    2017-05-01

    The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health. The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure. Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR 1  = 2.0 [1.0-3.9] and OR 2  = 7.6 [2.8-20.5]). The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Antidepressant, anxiolytic and anti-nociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch leaves in mice model

    Directory of Open Access Journals (Sweden)

    Mohammad Shah Hafez Kabir

    2015-11-01

    Full Text Available Objective: To estimate the antidepressant, anxiolytic and antinociceptive activities of ethanol extract of Steudnera colocasiifolia K. Koch (S. colocasiifolia leaves. Methods: Swiss albino mice treated with 1% Tween solution, standard drugs and ethanol extract of S. colocasiifolia, respectively, were subjected to the neurological and antinociceptive investigations. The tail suspension test and forced swimming test were used for testing antidepressant activity, where the parameter is the measurement of immobility time. Anxiolytic activity was evaluated by hole board model. Anti-nociceptive potential of the extract was also screened for centrally acting analgesic activity by using formalin induced licking response model and acetic acid induced writhing test was used for testing peripheral analgesic action. Results: Ethanol extract of S. colocasiifolia significantly decreased the period of immobility in both tested models (tail suspension and forced swimming models of antidepressant activity. In the hole board model, there was a dose dependant (at 100 and 200 mg/kg and a significant increase in the number of head dipping by comparing with control (1% Tween solution (P < 0.05 and P < 0.001. In formalin induced licking model, a significant inhibition of pain compared to standard diclofenac sodium was observed (P < 0.05 and P < 0.001. In acetic acid induced test, there was a significant reduction of writhing response and pain in mice treated with leaves extract of S. colocasiifolia at 200 mg/kg body weight (P < 0.05 and P < 0.001. Conclusions: The results proofed the prospective antidepressant, anxiolytic and antinociceptive activities of ethanol extract of S. colocasiifolia leaves.

  17. Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice.

    Science.gov (United States)

    Thompson, Trey; Grabowski-Boase, Laura; Tarantino, Lisa M

    2015-06-01

    Understanding and effectively treating anxiety disorders are a challenge for both scientists and clinicians. Despite a variety of available therapies, the efficacy of current treatments is still not optimal and adverse side effects can result in non-compliance. Animal models have been useful for studying the underlying biology of anxiety and assessing the anxiolytic properties of potential therapeutics. The open field (OF) is a commonly used assay of anxiety-like behavior. The OF was developed and validated in rats and then transferred to use in the mouse with only limited validation. The present study tests the efficacy of prototypical benzodiazepine anxiolytics, chlordiazepoxide (CDP) and diazepam (DZ), for increasing center time in the OF in C57BL/6J (B6) mice. Multiple doses of CDP and DZ did not change time spent in the center of the OF. Increasing illumination in the OF did not alter these results. The non-benzodiazepine anxiolytic, buspirone (BUSP) also failed to increase center time in the OF while the anxiogenic meta-chlorophenylpiperazine (mCPP) increased center time. Additional inbred mouse strains, BALB/cJ (BALB) and DBA/2J (D2) did not show any change in center time in response to CDP. Moreover, evaluation of CDP in B6 mice in the elevated plus maze (EPM), elevated zero maze (EZM) and light dark assay (LD) did not reveal changes in anxiety-like behavior while stress-induced hyperthermia (SIH) was decreased by DZ. Pharmacokinetic (PK) studies suggest that adequate CDP is present to induce anxiolysis. We conclude that the measure of center time in the OF does not show predictive validity for anxiolysis in these inbred mouse strains. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. alpha2-Adrenergic agonists antagonise the anxiolytic-like effect of antidepressants in the four-plate test in mice.

    Science.gov (United States)

    Massé, Fabienne; Hascoët, Martine; Bourin, Michel

    2005-10-14

    Selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs) has been reported to be efficient in anxiety disorders. Some animal models have demonstrated an anxiolytic-like effect following acute administration, however, it is not yet known how noradrenergic receptors are implicated in the therapeutic effects of antidepressants (ADs) in anxiety. The effects of two alpha(2)-adrenoceptor agonists (clonidine, guanabenz) on anxiolytic-like effect of two SSRIs (paroxetine and citalopram) and two SNRIs (venlafaxine and milnacipran) were evaluated in the four-plate test (FPT) in mice. Paroxetine (4 mg/kg), citalopram (8 mg/kg), venlafaxine (8 mg/kg), and milnacipran (8 mg/kg) administered intraperitoneally (i.p.) increased the number of punishments accepted by mice in the FPT. Clonidine (0.0039-0.5 mg/kg) and guanabenz (0.03-0.5mg/kg) had no effect on the number of punishments accepted by mice. Clonidine (0.03 and 0.06 mg/kg) and guanabenz (0.125 and 0.5 mg/kg) (i.p. -45 min) reversed the anti-punishment effect of paroxetine, citalopram, venlafaxine and milnacipran (i.p. -30 min). But if the antidepressants are administered 45 min before the test and alpha(2)-adrenoceptor agonists 30 min before the test, alpha(2)-adrenoceptor agonists failed to alter the anti-punishment effect of antidepressants. The results of this present study indicate that alpha(2)-adrenoceptor agonists antagonise the anxiolytic-like effect of antidepressants in mice when they are administered 15 min before the administration of antidepressant suggesting a close inter-regulation between noradrenergic and serotoninergic system in the mechanism of SSRIs and SNRIs in anxiety-like behaviour.

  19. Antidepressant and anxiolytic properties of the methanolic extract of Momordica charantia Linn (Cucurbitaceae) and its mechanism of action.

    Science.gov (United States)

    Ishola, I O; Akinyede, A A; Sholarin, A M

    2014-07-01

    The whole plant of Momordica charantia Linn (Cucurbitaceae) is used in traditional African medicine in the management of depressive illness. Momordica charantia (MC) (50-400 mg/kg, p.o.) was administered 1 h before behavioural studies using the forced swimming test (FST) and tail suspension test (TST) to investigate antidepressant-like effect while the anxiolytic-like effect was evaluated with elevated plus maze test (EPM), hole-board test (HBT), and light-dark test (LDT). Acute treatment with MC (50-400 mg/kg) significantly increased swimming time (86.51%) and reduced the duration of immobility (52.35%) in FST and TST with peak effects observed at 200 mg/kg, respectively, in comparison to control. The pretreatment of mice with either sulpiride (dopamine D2 receptor antagonist), or metergoline (5-HT2 receptor antagonist), or cyproheptadine (5-HT2 receptor antagonist), or prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), and atropine (muscarinic cholinergic receptor antagonist) 15 min before oral administration of MC (200 mg/kg) significantly blocked its anti-immobility effect. Similarly, MC (200 mg/kg) significantly reduced anxiety by increasing the open arm exploration (64.27%) in EPM, number of head-dips in HBT (34.38%), and time spent in light compartment (29.38%) in the LDT. However, pretreatment with flumazenil (GABAA receptor antagonist) 15 min before MC (200 mg/kg) significantly blocked (54.76%) its anxiolytic effect. The findings in this study showed that MC possesses antidepressant-like effect that is dependent on the serotonergic (5-HT2 receptor), noradrenergic (α1- and α2-adrenoceptors), dopaminergic (D2 receptor), and muscarinic cholinergic systems and an anxiolytic-like effect that might involve an action on benzodiazepine-type receptor. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Anxiolytic-like effect of Rauvolfia ligustrina Willd: ex Roem. & Schult., Apocynaceae, in the elevated plus-maze and hole-board tests

    Directory of Open Access Journals (Sweden)

    Sueli Mendonça Netto

    Full Text Available Rauvolfia ligustrina Willd. ex Roem. & Schult. (Apocynaceae, popularly known as "arrebenta-boi" and "paratudo". In behavioral screening ethanol extract of R. ligustrina roots demonstrated depressant effect on the CNS and anticonvulsant properties. The purpose of this study was to characterize the putative anxiolytic-like effects of the ethanol extract of Rauvolfia ligustrina roots (EER using the elevated plus maze (EPM and the hole-board apparatus in rodents. This extract, administered intraperitoneally, in different doses (3.9, 7.8 and 15.6 mg/kg was able to increase significantly the number of entries (p < 0.05, as well as the time spent in the open arms of the EPM, indicating an anxiolytic-like effect. Additionally, EER-treated (3.9 and 7.8 mg/kg increased significantly the number of border visit and head-dipping. This data suggest an anxiolytic effect of EER in animal models of anxiety.

  1. Mexican medicinal plants with anxiolytic or antidepressant activity: Focus on preclinical research.

    Science.gov (United States)

    López-Rubalcava, Carolina; Estrada-Camarena, Erika

    2016-06-20

    of the mechanism of action is inconclusive. The need for systematic studies in preclinical and clinical research is evident, and efforts should be done to fulfill these research. Finally, it is important also to study possible drug-herbal interactions to establish specific recommendations for people that use these plants as anxiolytic or antidepressant treatments either alone or in combination with another type of medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action

    DEFF Research Database (Denmark)

    Fitzpatrick, Ciarán Martin; Larsen, Maria; Madsen, Louise

    2016-01-01

    serotonin reuptake inhibitor (SSRI) citalopram (0-10 mg/kg) was investigated in mice, using the APAM LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed with the forced swim test (FST), while anxiolytic-like effects were tested with the elevated zero maze (EZM) and the marble burying test (MBT...... the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression, as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have...

  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. GABA-A Receptor Modulation and Anticonvulsant, Anxiolytic, and Antidepressant Activities of Constituents from Artemisia indica Linn

    Directory of Open Access Journals (Sweden)

    Imran Khan

    2016-01-01

    Full Text Available Artemisia indica, also known as “Mugwort,” has been widely used in traditional medicines. However, few studies have investigated the effects of nonvolatile components of Artemisia indica on central nervous system’s function. Fractionation of Artemisia indica led to the isolation of carnosol, ursolic acid, and oleanolic acid which were evaluated for their effects on GABA-A receptors in electrophysiological studies in Xenopus oocytes and were subsequently investigated in mouse models of acute toxicity, convulsions (pentylenetetrazole induced seizures, depression (tail suspension and forced swim tests, and anxiety (elevated plus maze and light/dark box paradigms. Carnosol, ursolic acid, and oleanolic acid were found to be positive modulators of α1β2γ2L GABA-A receptors and the modulation was antagonized by flumazenil. Carnosol, ursolic acid, and oleanolic acid were found to be devoid of any signs of acute toxicity (50–200 mg/kg but elicited anticonvulsant, antidepressant, and anxiolytic activities. Thus carnosol, ursolic acid, and oleanolic acid demonstrated CNS activity in mouse models of anticonvulsant, antidepressant, and anxiolysis. The anxiolytic activity of all three compounds was ameliorated by flumazenil suggesting a mode of action via the benzodiazepine binding site of GABA-A receptors.

  5. Acute food deprivation separates motor-activating from anxiolytic effects of caffeine in a rat open field test model.

    Science.gov (United States)

    Schulz, Daniela

    2018-03-14

    Similar doses of caffeine have been shown to produce either anxiolytic or anxiogenic effects in rats. The reasons for these conflicting results are not known. We hypothesized that food deprivation stress interacts with the stimulant effects of caffeine to increase anxiety-like behavior. We tested 32 female Sprague Dawley rats in a dim open field for 10 min. Half of the animals were food deprived for 24 h and injected (intraperitoneal) with caffeine (30 mg/kg; n=7) or deionized water (n=8) 20 min before the open field test. The other half was nondeprived and injected with caffeine (30 mg/kg; n=8) or deionized water (n=9). Results showed that nondeprived rats injected with caffeine moved longer distances and at a greater speed in the periphery and moved longer distances and spent more time in the center than rats treated with vehicle, indicative of motor-activating and/or anxiolytic effects of caffeine. Rats that were food deprived and injected with caffeine moved longer distances in the center and tended to spend more time there, indicative of anxiolysis. We conclude that caffeine had two effects on behavior, motor activation and a reduction of anxiety, and that food deprivation separated these effects.

  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. A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin.

    Science.gov (United States)

    Benammi, Hind; El Hiba, Omar; Romane, Abderrahmane; Gamrani, Halima

    2014-06-01

    Anxiety is one of the most common mental disorders sharing extreme or pathological anxiety states as the primary disturbance in mood or emotional tone, with increased fear and exaggerated acute stress responses. Medicinal plants are very variable, but some of them are used as a spice such as curcumin (Curcuma longa). Curcumin shows a wide range of pharmacological potentialities, however, little is known about its anxiolytic properties. The aim of our study was to assess the anti-anxiety potential of curcumin extract against experimental lead induced-anxiety in rats. Experiments were carried out on male Wistar rats intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using immunohistochemistry and anxiety assessment tests (dark light box and elevated plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results showed, for the first time, a noticeable anxiolytic effect of curcumin against lead induced anxiety in rats and this may possibly result from modulation of central neuronal monoaminergic neurotransmission, especially serotonin, which has shown a significant reduction of the immunoreactivity within the DRN. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. Evaluation of the analgesic, sedative-anxiolytic, cytotoxic and thrombolytic potentials of the different extracts of Kalanchoe pinnata leaves

    Directory of Open Access Journals (Sweden)

    Md. Razibul Habib

    2015-12-01

    Full Text Available Objective: To evaluate the analgesic, neuropharmacological, cytotoxic and thrombolytic potentials of the aqueous, ethanol and ethyl acetate extracts of Kalanchoe pinnata leaves. Methods: At the dose of 400 mg/kg body weight, the analgesic activity of the extracts were evaluated by the acetic acid-induced writhing and formalin-induced persistent pain tests while neuropharmacological activity was evaluated by the open field, hole cross and elevated plus maze tests. The cytotoxic potential was observed by brine shrimp lethality bioassay and the thrombolytic potential was investigated by clot lysis test. Results: The aqueous extract significantly suppressed the number of writhing (96.78% as well as the formalin-induced persistent pain on the early phase (46.92% and on the late phase (40.98%. Again in case of hole cross and open field tests, the locomotor activity was decreased significantly (P < 0.001 mostly by the ethyl acetate extract. Furthermore, the sedative-anxiolytic activity was supported by the increased percent (P < 0.01 of frequency into the open arm on elevated plus maze test. Besides, the extracts showed moderate lethality and thrombolytic activity. Conclusions: The findings showed that activities are comparable to the standards and in some cases are stronger than the standards. Therefore, based on the results, it is evident that it has great analgesic and sedative-anxiolytic activity with moderate cytotoxic and thrombolytic potential.

  9. Profile of Antiemetic Activity of Netupitant Alone or in Combination with Palonosetron and Dexamethasone in Ferrets and Suncus murinus (house musk shrew

    Directory of Open Access Journals (Sweden)

    John A Rudd

    2016-08-01

    Full Text Available Background and Aims: Chemotherapy-induced acute and delayed emesis involves the activation of multiple pathways, with 5-hydroxytryptamine (5-HT; serotonin playing a major role in the initial response. Substance P tachykinin NK1 receptor antagonists can reduce emesis induced by disparate emetic challenges and therefore have a clinical utility as broad inhibitory anti-emetic drugs. In the present studies, we investigate the broad inhibitory anti-emetic profile of a relatively new NK1 receptor antagonist, netupitant, alone or in combination with the long acting 5-HT3 receptor antagonist, palonosetron, for a potential to reduce emesis in ferrets and shrews.Materials and Methods: Ferrets were pretreated with netupitant and/or palonosetron, or their combination, and then administered apomorphine (0.125 mg/kg, s.c., morphine (0.5 mg/kg, s.c., ipecacuanha (1.2 mg/kg, p.o., copper sulphate (100 mg/kg, intragastric, or cisplatin (5-10 mg/kg, i.p.; in other studies netupitant was administered to Suncus murinus before motion (4 cm horizontal displacement, 2 Hz for 10 min.Results: Netupitant (3 mg/kg, p.o. abolished apomorphine-, morphine-, ipecacuanha- and copper sulphate-induced emesis. Lower doses of netupitant (0.03-0.3 mg/kg, p.o. dose-dependently reduced cisplatin (10 mg/kg, i.p.-induced emesis in an acute (8 h model, and motion-induced emesis in Suncus murinus. In a ferret cisplatin (5 mg/kg, i.p.-induced acute and delayed emesis model, netupitant administered once at 3 mg/kg, p.o., abolished the first 24 h response and reduced the 24-72 h response by 94.6 %; the reduction was markedly superior to the effect of a three times per day administration of ondansetron (1 mg/kg, i.p.. A single administration of netupitant (1 mg/kg, p.o. plus palonosetron (0.1 mg/kg, p.o. combined with dexamethasone (1 mg/kg, i.p., once per day, also significantly antagonized cisplatin-induced acute and delayed emesis and was comparable with a once-daily regimen of

  10. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    Science.gov (United States)

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  11. The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass).

    Science.gov (United States)

    Costa, Celso A Rodrigues de Almeida; Kohn, Daniele Oliveira; de Lima, Valéria Martins; Gargano, André Costa; Flório, Jorge Camilo; Costa, Mirtes

    2011-09-01

    The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system. The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT(1A) receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment. The present work found anxiolytic-like activity of the EO at the dose of 10mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LDB, indicating that the EO activity occurs via the GABA(A) receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus. The results corroborate the use of Cymbopogon citratus in folk medicine and

  12. A prospective cohort study of patient-reported vomiting, retching, nausea and antiemetic use during neoadjuvant long-course radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kristopher Dennis

    2018-03-01

    Full Text Available Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%, retching by 5(15% and nausea by 21(64%. No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days. There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting

  13. 5-HT1A receptor blockade reverses GABA(A) receptor alpha(3) subunit-mediated anxiolytic effects on stress-induced hyperthermia

    NARCIS (Netherlands)

    Vinkers, Christiaan H.; van Oorschot, Ruud; Korte, S. Mechiel; Olivier, Berend; Groenink, Lucianne

    Stress-related disorders are associated with dysfunction of both serotonergic and GABAergic pathways, and clinically effective anxiolytics act via both neurotransmitter systems. As there is evidence that the GABA(A) and the serotonin receptor system interact, a serotonergic component in the

  14. Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze.

    Science.gov (United States)

    Holmes, A; Rodgers, R J

    1999-11-01

    It has been widely reported that the anxiolytic efficacy of benzodiazepines in the elevated plus-maze test is abolished in subjects (rats or mice) that have been given a single prior undrugged experience of the test apparatus. The present series of experiments was designed to further characterise the key experiential determinants of this intriguing phenomenon in Swiss Webster mice. Using a standard 5 min test duration for both trials, Experiment 1 confirmed the anxiolytic efficacy of chlordiazepoxide (CDP; 5-20 mg/kg) in mice naive to the plus-maze, but a virtual elimination of drug effects in animals that had been pre-exposed to the maze 24 h earlier. Experiments 2 and 3 demonstrated that, while extending the duration of initial exposure to 10 min did not prevent the loss of CDP (10 mg/kg) efficacy in a standard-duration second trial, increasing the duration of both trials reinstated an anxiolytic profile for the compound. Finally, although trial 1 confinement to an open arm did not compromise CDP efficacy when animals were subsequently allowed to freely explore the maze (Experiment 4), closed arm confinement during initial exposure abolished the drug's anxiolytic action upon retest (Experiment 5). In contrast to previous findings in rats, these data suggest that the experientially induced loss of benzodiazepine efficacy in the mouse plus-maze depends rather critically upon prior discovery and exploration of relatively safe areas of the maze (i.e. closed arms). Results are discussed in relation to the hypothesis that the absence of an anxiolytic response to benzodiazepines in plus-maze-experienced subjects reflects the acquisition of an open arm phobia during trial 1.

  15. Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life.

    Science.gov (United States)

    Zuardi, Antonio W; Rodrigues, Natália P; Silva, Angélica L; Bernardo, Sandra A; Hallak, Jaime E C; Guimarães, Francisco S; Crippa, José A S

    2017-01-01

    The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

  16. The anxiolytic-like effect of 6-styryl-2-pyrone in mice involves GABAergic mechanism of action.

    Science.gov (United States)

    Chaves, Edna Maria Camelo; Honório-Júnior, Jose Eduardo Ribeiro; Sousa, Caren Nádia Soares; Monteiro, Valdécio Silveira; Nonato, Dayanne Terra Tenório; Dantas, Leonardo Pimentel; Lúcio, Ana Silvia Suassuna Carneiro; Barbosa-Filho, José Maria; Patrocínio, Manoel Cláudio Azevedo; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2018-02-01

    The present work aims to investigate the anxiolytic activity of 6-styryl-2-pyrone (STY), obtained from Aniba panurensis, in behavioral tests and amino acids dosage on male Swiss mice. The animals were treated with STY (1, 10 or 20 mg), diazepam (DZP 1 or 2 mg/kg) or imipramine (IMI 30 mg/kg). Some groups were administered with flumazenil, 30 min before administration of the STYor DZP. The behavioral tests performed were open field, rota rod, elevated plus maze (EPM), hole-board (HB) and tail suspension test (TST). After behavioral tests, these animals were sacrificed and had their prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) dissected for assaying amino acids (aspartate- ASP, glutamate- GLU, glycine- GLY, taurine- TAU and Gamma-aminobutyric acid- GABA). In EPM test, STY or DZP increased the number of entries and the time of permanence in the open arms, but these effects were reverted by flumazenil. In the HB test, STY increased the number of head dips however this effect was blocked by flumazenil. The effects of the STY on amino acid concentration in PFC showed increased GLU, GABA and TAU concentrations. In hippocampus, STY increased the concentrations of all amino acids studied. In striatum, STY administration at lowest dose reduced GLU concentrations, while the highest dosage caused the opposite effect. GLI, TAU and GABA concentrations increased with STY administration at highest doses. In conclusion, this study showed that STY presents an anxiolytic-like effect in behavioral tests that probably is related to GABAergic mechanism of action.

  17. Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

    Science.gov (United States)

    Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Matos, Natália Castelo Branco; de Freitas, Rayanne Brito; Lima, Nycole Brito Cortez; Patrocínio, Manoel Cláudio Azevedo; Leal, Luzia Kalyne Almeida Moreira; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2017-01-01

    Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

  18. Search for new potential anticonvulsants with anxiolytic and antidepressant properties among derivatives of 4,4-diphenylpyrrolidin-2-one.

    Science.gov (United States)

    Malawska, Katarzyna; Rak, Aleksandra; Gryzło, Beata; Sałat, Kinga; Michałowska, Małgorzata; Żmudzka, Elżbieta; Lodarski, Krzysztof; Malawska, Barbara; Kulig, Katarzyna

    2017-02-01

    The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction. The obtained compounds were assessed and tested for their anticonvulsant activity in two screening mouse models of seizures, i.e., the maximal electroshock (MES) test and in the subcutaneous pentylenetetrazole (scPTZ) test. The effect of these compounds on animals' motor coordination was measured in the rotarod test. A selected 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) was evaluated in vivo for its anxiolytic- and antidepressant-like properties. Its impact on animals' locomotor activity was also evaluated. Compound 8 showed protection (25%) in the MES and in the scPTZ tests at the dose of 100mg/kg and was not neurotoxic. In the four-plate test, compound 8 at the dose of 30mg/kg showed a statistically significant (p<0.05) anxiolytic-like activity. In the forced swim test, it reduced the immobility time by 24.3% (significant at p<0.05), which indicates its potential antidepressant-like properties. In the locomotor activity test, compound 8 significantly reduced animals' locomotor activity by 79.9%. The results obtained make a new derivative of 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) a promising lead structure for further development. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  19. Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

    Science.gov (United States)

    Burda-Malarz, Kinga; Kus, Krzysztof; Ratajczak, Piotr; Czubak, Anna; Hardyk, Szymon; Nowakowska, Elżbieta

    2014-07-01

    Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

  20. Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons

    International Nuclear Information System (INIS)

    Witkin, J.M.; Mansbach, R.S.; Barrett, J.E.; Bolger, G.T.; Skolnick, P.; Weissman, B.

    1987-01-01

    Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of [ 3 H]-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected [ 3 H]-5-HT binding and none of the compounds appreciably inhibited uptake of [ 3 H]-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited [ 3 H]ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of [ 3 H]ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum

  1. Administration of riluzole into the basolateral amygdala has an anxiolytic-like effect and enhances recognition memory in the rat.

    Science.gov (United States)

    Sugiyama, Azusa; Saitoh, Akiyoshi; Yamada, Misa; Oka, Jun-Ichiro; Yamada, Mitsuhiko

    2017-06-01

    It is widely thought that inactivation of the glutamatergic system impairs recognition memory in rodents. However, we previously demonstrated that systemic administration of riluzole, which blocks the glutamatergic system, enhances recognition memory in the rat novel object recognition (NOR) test. The mechanisms underlying this paradoxical effect of riluzole on recognition memory remain unclear. In the present study, adult male Wistar rats were bilaterally cannulated in the basolateral amygdala (BLA) to examine the effects of intra-BLA administration of riluzole. We also compared the effects of riluzole with those of d-cycloserine, a partial agonist at the glycine binding site on the N-methyl-d-aspartate (NMDA) receptor. The BLA plays a critical role not only in recognition memory, but also in the regulation of anxiety. In the present study, intra-BLA administration of riluzole or d-cycloserine enhanced recognition memory in the NOR test. It was previously suggested that recognition memory can be strongly affected by the state of anxiety in rodents. Interestingly, intra-BLA administration of riluzole, but not d-cycloserine, produced a potent anxiolytic-like effect in the elevated plus-maze test. Thus, the enhancement of recognition memory by riluzole might be an indirect effect resulting from the anxiolytic-like action of the intra-BLA administration of the drug, and may not be directly related to inhibition of the glutamatergic system. Further studies are needed to clarify the mechanisms underlying the memory enhancing effect of riluzole. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life

    Directory of Open Access Journals (Sweden)

    Antonio W. Zuardi

    2017-05-01

    Full Text Available The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg, and CBD (100, 300, and 900 mg. The subjects were underwent a test of public speaking in a real situation (TPSRS where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes after administration of the drug/placebo, as time 0: -5 (baseline, 80 (pre-test, 153 (speech, and 216 (post-speech. Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

  3. A Novel Integrative Mechanism in Anxiolytic Behavior Induced by Galanin 2/Neuropeptide Y Y1 Receptor Interactions on Medial Paracapsular Intercalated Amygdala in Rats

    Directory of Open Access Journals (Sweden)

    Manuel Narváez

    2018-05-01

    Full Text Available Anxiety is evoked by a threatening situation and display adaptive or defensive behaviors, found similarly in animals and humans. Neuropeptide Y (NPY Y1 receptor (NPYY1R and Galanin (GAL receptor 2 (GALR2 interact in several regions of the limbic system, including the amygdala. In a previous study, GALR2 enhanced NPYY1R mediated anxiolytic actions on spatiotemporal parameters in the open field and elevated plus maze, involving the formation of GALR2/NPYY1R heteroreceptor complexes in the amygdala. Moreover, the inclusion of complementary ethological parameters provides a more comprehensive profile on the anxiolytic effects of a treatment. The purpose of the current study is to evaluate the anxiolytic effects and circuit activity modifications caused by coactivation of GALR2 and NPYY1R. Ethological measurements were performed in the open field, the elevated plus-maze and the light-dark box, together with immediate early gene expression analysis within the amygdala-hypothalamus-periaqueductal gray (PAG axis, as well as in situ proximity ligation assay (PLA to demonstrate the formation of GALR2/NPYY1R heteroreceptor complexes. GALR2 and NPYY1R coactivation resulted in anxiolytic behaviors such as increased rearing and head-dipping, reduced stretch attend postures and freezing compared to single agonist or aCSF injection. Neuronal activity indicated by cFos expression was decreased in the dorsolateral paracapsular intercalated (ITCp-dl subregion of the amygdala, ventromedial hypothalamic (VMH nucleus and ventrolateral part of the periaqueductal gray (vlPAG, while increased in the perifornical nucleus of the hypothalamus (PFX following coactivation of GALR2 and NPYY1R. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was explicitly observed in ITCp-dl, following GALR2 and NPYY1R coactivation. Besides, knockdown of GALR2 was found to reduce the density of complexes in ITCp-dl. Taken together, these results open up the possibility

  4. Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.

    Science.gov (United States)

    Kitazaki, Takeshi; Fukuda, Yuichi; Fukahori, Susumu; Oyanagi, Kazuhiko; Soda, Hiroshi; Nakamura, Yoichi; Kohno, Shigeru

    2015-01-01

    The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.

  5. Study on the interactions of antiemetic drugs and 12-tungstophosphoric acid by absorption and resonance Rayleigh scattering spectra and their analytical applications

    Science.gov (United States)

    Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Hu, Xiaoli

    2013-03-01

    In 0.1 mol L-1 HCl medium, antiemetic drugs (ATM), such as granisetron hydrochloride (GS) and tropisetron hydrochloride (TS), reacted with H3PW12O40·nH2O and formed 3:1 ion-association complex of [(ATM)3PW12O40], then self-aggregated into nanoparticles-[(ATM)3PW12O40]n with an average size of 100 nm. The reaction resulted in the enhancement of resonance Rayleigh scattering (RRS) and the absorption spectra. The increments of scattering intensity (ΔIRRS) and the change of absorbance (ΔA) were both directly proportional to the concentrations of ATM in certain ranges. Accordingly, two new RRS and spectrophotometric methods were proposed for ATM detection. The detection limits (3σ) of GS and TS were 3.2 ng mL-1 and 4.0 ng mL-1(RRS method), 112.5 ng mL-1 and 100.0 ng mL-1(spectrophotometric method). These two methods were applied to determine GS in orally disintegrating tablets and the results were in good agreement with the official method. The ground-state geometries and electronic structures of GS and TS were optimized by the hybrid density functional theory (DFT) method and the shape of [(ATM)3PW12O40]n was characterized by atomic force microscopy (AFM). Take the RRS method with higher sensitivity as an example, the reaction mechanism and the reasons for enhancement of scattering were discussed.

  6. Retrospective Chart Review of Skin-to-Skin Contact in the Operating Room and Administration of Analgesic and Anxiolytic Medication to Women After Cesarean Birth.

    Science.gov (United States)

    Wagner, Debra L; Lawrence, Stephen; Xu, Jing; Melsom, Janice

    2018-04-01

    Transporting a newborn out of the operating room after cesarean birth can contribute to maternal awareness of discomfort, anxiety, and the need for administration of analgesics and anxiolytics for relief. This retrospective study analyzed the association between skin-to-skin contact in the operating room and administration of analgesics and anxiolytics to women in the operating and recovery rooms after cesarean birth. Our results indicated a trend toward decreased medication administration for women who experienced skin-to-skin contact and add to evidence supporting the incorporation of skin-to-skin contact in the operating room as the standard of care for cesarean birth. This practice has the potential to enhance the birth experience, promote breastfeeding, and provide greater safety with less exposure to opioids and benzodiazepines for women and their newborns. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  7. Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats.

    Science.gov (United States)

    Sharma, Ajaykumar N; Pise, Ashish; Sharma, Jay N; Shukla, Praveen

    2015-06-01

    Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence.

  8. Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia.

    Science.gov (United States)

    Diemer, Julia; Domschke, Katharina; Mühlberger, Andreas; Winter, Bernward; Zavorotnyy, Maxim; Notzon, Swantje; Silling, Karen; Arolt, Volker; Zwanzger, Peter

    2013-11-01

    Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  9. Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents.

    Science.gov (United States)

    Correa, M; Manrique, H M; Font, L; Escrig, M A; Aragon, C M G

    2008-11-01

    Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats. The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis. The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D: -penicillamine (50 mg/kg, IP) on the plus maze. SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol. Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.

  10. Anxiolytic-like actions of the hexane extract from leaves of Annona cherimolia in two anxiety paradigms: possible involvement of the GABA/benzodiazepine receptor complex.

    Science.gov (United States)

    López-Rubalcava, C; Piña-Medina, B; Estrada-Reyes, R; Heinze, G; Martínez-Vázquez, M

    2006-01-11

    A hexane extract of leaves of Annona cherimolia produced anxiolytic-like actions when administered to mice and tested in two animal models of anxiety: the mouse avoidance exploratory behavior and the burying behavior tests. In order to discard unspecific drug-actions on general activity, all treatments studied in the anxiety paradigms were also analyzed in the open field test. Results showed that A. cherimolia induced anxiolytic-like actions at the doses of 6.25, 12.5, 25.0 and 50.0 mg/kg. Picrotoxin (0.25 mg/kg), a GABA-gated chloride ion channel blocker, antagonized the anxiolytic-like actions of A. cherimolia, while a sub-effective dose of muscimol (0.5 mg/kg), a selective GABA(A) receptor agonist, facilitated the effects of a sub-optimal dose of A. cherimolia (3.12 mg/kg). Thus, the involvement of the GABA(A) receptor complex in the anxiolytic-like actions of A. cherimolia hexane extract is suggested. In addition the extract was also able to enhance the duration of sodium pentobarbital induced sleeping time. Taken together, results indicate that the hexane extract of A. cherimolia has depressant activity on the Central Nervous System and could interact with the GABA(A) receptor complex. On the other hand, the chromatographic separation of this extract led to the isolation of palmitone, and beta-sitosterol as major constituents. In addition a GC-MS study of some fractions revealed the presence of several compounds such beta-cariophyllene, beta-selinene, alpha-cubebene, and linalool that have been reported to show effects on behavior that could explain some of the extract effects.

  11. Nausea still the poor relation in antiemetic therapy? The impact on cancer patients' quality of life and psychological adjustment of nausea, vomiting and appetite loss, individually and concurrently as part of a symptom cluster.

    Science.gov (United States)

    Pirri, Carlo; Bayliss, Evan; Trotter, James; Olver, Ian N; Katris, Paul; Drummond, Peter; Bennett, Robert

    2013-03-01

    Despite significant antiemetic advances, almost 50% of treated cancer patients still experience nausea and vomiting (N&V). The goal of antiemetic therapy--complete prevention of treatment-induced nausea and/or vomiting (TIN+/-V)--remains elusive for several reasons. Potentially, N&V may be part of a symptom cluster where co-occurring symptoms negatively affect antiemetic management. Consequently, we examined TIN+/-V incidence and the impact of nausea, vomiting and symptom cluster(s) containing them, respectively, on patients' quality of life (QoL) and psychological adjustment across treatment. A longitudinal secondary analysis was performed on data from a prospective, observational QoL study involving 200 newly diagnosed cancer patients who underwent combined modality treatment. QoL, psychological adjustment and patient/clinical characteristics were examined at pretreatment, on-treatment (8 weeks) and post-treatment. Overall, 62% of patients experienced TIN+/-V, with TIN (60%) doubling TIV incidence (27 %). Exploratory factor analyses of QoL scores at each treatment time point identified a recurrent gastrointestinal symptom cluster comprising nausea, vomiting and appetite loss. Approximately two thirds of patients reported co-occurrence of all three symptoms, which exerted synergistic effects of multiplicative proportions on overall QoL. Patients who reported co-occurrence of these symptoms during treatment experienced significantly greater QoL impairment (physical, role and social functioning, fatigue, N&V, appetite loss, overall physical health, overall QOL) and psychological distress (cancer distress, premorbid neuroticism) than those unaffected (0.001 > p ≤ 0.05). Moreover, nausea was more pervasive than vomiting or appetite loss across treatment and had a greater impact on overall QoL. While antiemetic therapy was effective for vomiting and helped prevent/relieve associated appetite loss, the benefits for appetite loss were seemingly constrained by its

  12. Anxiolytic-like effect of inhalation of essential oil from Lavandula officinalis: investigation of changes in 5-HT turnover and involvement of olfactory stimulation.

    Science.gov (United States)

    Takahashi, Mizuho; Yamanaka, Ayako; Asanuma, Chihiro; Asano, Hiroko; Satou, Tadaaki; Koike, Kazuo

    2014-07-01

    Essential oil extracted from Lavandula officinalis (LvEO) has a long history of usage in anxiety alleviation with good evidence to support its use. However, findings and information regarding the exact pathway involved and mechanism of action remain inconclusive. Therefore, we aimed to (1) reveal the influence of olfactory stimulation, and (2) determine whether the serotonergic system is involved in the anxiolytic effect of LvEO when it is inhaled. To this end, we first compared the anxiety-related behaviors of normosmic and anosmic mice. LvEO inhalation caused notable elevation in anxiety-related parameters with or without olfactory perception, indicating that olfactory stimulation is not necessarily required for LvEO to be effective. Neurochemical analysis of the serotonin (5-HT) turnover rate, accompanied by EPM testing, was then performed. LvEO significantly increased the striatal and hippocampal levels of 5-HT and decreased turnover rates in accordance with the anxiolytic behavioral changes. These results, together with previous findings, support the hypothesis that serotonergic neurotransmission plays a certain role in the anxiolytic properties of LvEO.

  13. Caffeine prevents high-intensity exercise-induced increase in enzymatic antioxidant and Na+-K+-ATPase activities and reduction of anxiolytic like-behaviour in rats.

    Science.gov (United States)

    Vieira, Juliano M; Carvalho, Fabiano B; Gutierres, Jessié M; Soares, Mayara S P; Oliveira, Pathise S; Rubin, Maribel A; Morsch, Vera M; Schetinger, Maria Rosa; Spanevello, Roselia M

    2017-11-01

    Here we investigated the impact of chronic high-intensity interval training (HIIT) and caffeine consumption on the activities of Na + -K + -ATPase and enzymes of the antioxidant system, as well as anxiolytic-like behaviour in the rat brain. Animals were divided into groups: control, caffeine (4 mg/kg), caffeine (8 mg/kg), HIIT, HIIT plus caffeine (4 mg/kg) and HIIT plus caffeine (8 mg/kg). Rats were trained three times per week for 6 weeks, and caffeine was administered 30 minutes before training. We assessed the anxiolytic-like behaviour, Na + -K + -ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in the brain. HIIT-induced anxiolytic-like behaviour increased Na + -K + -ATPase and GPx activities and TBARS levels, altered the activities of SOD and CAT in different brain regions, and decreased GSH levels. Caffeine, however, elicited anxiogenic-like behaviour and blocked HIIT effects. The combination of caffeine and HIIT prevented the increase in SOD activity in the cerebral cortex and GPx activity in three brain regions. Our results show that caffeine promoted anxiogenic behaviour and prevented HIIT-induced changes in the antioxidant system and Na + -K + -ATPase activities.

  14. [The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c mice: nootropic and anxiolytic effects].

    Science.gov (United States)

    Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

    2013-01-01

    The influence of acute and long-term piracetam administration on the dynamics of rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug effects, as well as on their interrelation with NMDA- and BDZ-receptors was studied in inbred mice strains differing in cognitive and emotional status--C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c strain was used as a model of psychopathology, combining increased anxiety and cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p. injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor density and slow escalation of the specific nootropic effect was observed in BALB/c mice. Non-specific anxiolytic effects in these mice increased for the first 1 - 7 days without any changes in BDZ-binding and then decreased to initial values accompanied by decrement of brain receptor concentration. Thus, in BALB/c mice, a slowly manifested specific nootropic action of piracetam develops, following an increase in NMDA receptor density, whereas the non-specific anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

  15. 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

  16. Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.

    Science.gov (United States)

    Ceremuga, Tomás Eduardo; Helmrick, Katie; Kufahl, Zachary; Kelley, Jesse; Keller, Brian; Philippe, Fabiola; Golder, James; Padrón, Gina

    As the use of herbal medications continues to increase in America, the potential interaction between herbal and prescription medications necessitates the discovery of their mechanisms of action. The purpose of this study was to investigate the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the γ-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective, between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin, curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing was performed using the elevated plus maze, open field test, and forced swim test. A 2-tailed multivariate analysis of variance and least significant difference post hoc tests were used for data analysis. In our models, curcumin did not demonstrate anxiolytic effects or changes in behavioral despair. An interaction of curcumin at the benzodiazepine site of the GABAA receptor was also not observed. Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems.

  17. A cost-utility analysis of risk model-guided versus physician's choice antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer: a net benefit regression approach.

    Science.gov (United States)

    Thavorn, Kednapa; Coyle, Doug; Hoch, Jeffrey S; Vandermeer, Lisa; Mazzarello, Sasha; Wang, Zhou; Dranitsaris, George; Fergusson, Dean; Clemons, Mark

    2017-08-01

    We assessed the cost-effectiveness of a risk model-guided (RMG) antiemetic prophylaxis strategy compared with the physician's choice (PC) strategy in patients receiving chemotherapy for early-stage breast cancer. We conducted a cost-utility analysis based on a published randomized controlled trial of 324 patients with early-stage breast cancer undergoing chemotherapy at two Canadian cancer centers. Patients were randomized to receive their antiemetic treatments according to either predefined risk scores or the treating physician's preference. Effectiveness was measured as quality-adjusted life years (QALYs) gained. Cost and utility data were obtained from the Canadian published literature. We used generalized estimating equations to estimate the incremental cost-effectiveness ratios (ICERs) and 95% confidence intervals (CIs) over a range of willingness-to-pay values. The lower and upper bounds of the 95% CIs were used to characterize the statistical uncertainty for the cost-effectiveness estimates and construct cost-effectiveness acceptability curves. From the health care system's perspective, the RMG strategy was associated with greater QALYs gained (0.0016, 95% CI 0.0009, 0.0022) and higher cost ($49.19, 95% CI $24.87, $73.08) than the PC strategy, resulting in an ICER of $30,864.28 (95% CI $14,718.98, $62,789.04). At the commonly used threshold of $50,000/QALY, the probability that RMG prophylaxis is cost-effective was >94%; this probability increased with greater willingness-to-pay values. The risk-guided antiemetic prophylaxis is an economically attractive option for patients receiving chemotherapy for early-stage breast cancer. This information supports the implementation of risk prediction models to guide chemotherapy-induced nausea and vomiting prophylaxis in clinical practices.

  18. Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice.

    Directory of Open Access Journals (Sweden)

    Maxime Cazorla

    Full Text Available In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders.

  19. Analysis of the anxiolytic-like effect of TRH and the response of amygdalar TRHergic neurons in anxiety.

    Science.gov (United States)

    Gutiérrez-Mariscal, Mariana; de Gortari, Patricia; López-Rubalcava, Carolina; Martínez, Adrián; Joseph-Bravo, Patricia

    2008-02-01

    Thyrotropin-releasing hormone (TRH) was first described for its neuroendocrine role in controlling the hypothalamus-pituitary-thyroid axis (HPT). Anatomical and pharmacological data evidence its participation as a neuromodulator in the central nervous system. Administration of TRH induces various behavioural effects including arousal, locomotion, analepsy, and in certain paradigms, it reduces fear behaviours. In this work we studied the possible involvement of TRHergic neurons in anxiety tests. We first tested whether an ICV injection of TRH had behavioural effects on anxiety in the defensive burying test (DBT). Corticosterone serum levels were quantified to evaluate the stress response and, the activity of the HPT axis to distinguish the endocrine response of TRH injection. Compared to a saline injection, TRH reduced cumulative burying, and decreased serum corticosterone levels, supporting anxiolytic-like effects of TRH administration. The response of TRH neurons was evaluated in brain regions involved in the stress circuitry of animals submitted to the DBT and to the elevated plus maze (EPM), tests that allow to correlate biochemical parameters with anxiety-like behaviour. In the DBT, the response of Wistar rats was compared with that of the stress-hypersensitive Wistar Kyoto (WKY) strain. Behavioural parameters were analysed in recorded videos. Animals were sacrificed 30 or 60min after test completion. In various limbic areas, the relative mRNA levels of TRH, its receptors TRH-R1 and -R2, and its inactivating ectoenzyme pyroglutamyl peptidase II (PPII), were determined by RT-PCR, TRH tissue content by radioimmunoassay (RIA). The extent of the stress response was evaluated by measuring the expression profile of CRH, CRH-R1 and GR mRNA in the paraventricular nucleus (PVN) of the hypothalamus and in amygdala, corticosterone levels in serum. As these tests demand increased physical activity, the response of the HPT axis was also evaluated. Both tasks increased the

  20. 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

  1. Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

    Directory of Open Access Journals (Sweden)

    Wang Jia

    2009-11-01

    Full Text Available Abstract Background Protein kinase C interacting protein (PKCI/HINT1 is a small protein belonging to the histidine triad (HIT family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Results Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST and the tail suspension (TST tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. Conclusion PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.

  2. Genetic ablation of the GluK4 kainate receptor subunit causes anxiolytic and antidepressant-like behavior in mice.

    Science.gov (United States)

    Catches, Justin S; Xu, Jian; Contractor, Anis

    2012-03-17

    There is a clear link between dysregulation of glutamatergic signaling and mood disorders. Genetic variants in the glutamate receptor gene GRIK4, which encodes the kainate receptor subunit GluK4, alter the susceptibility for depression, bipolar disorder and schizophrenia. Here we demonstrate that Grik4(-/-) mice have reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, Grik4(-/-) mice spent significantly more time exploring the open areas of the maze. In anxiogenic tests of marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim test, a test of learned helplessness that is used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting that Grik4 ablation has an antidepressant-like effect. Finally, in the sucrose preference test, a test for anhedonia in rodents, Grik4(-/-) mice demonstrated increased sucrose preference. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs are known to modulate synaptic plasticity. We tested whether Grik4 ablation had effects on mossy fiber (MF) plasticity and found there to be a significant impairment in LTP likely through a loss of KAR modulation of excitability of the presynaptic MF axons. These studies demonstrate a clear anxiolytic and antidepressant phenotype associated with ablation of Grik4 and a parallel disruption in hippocampal plasticity, providing support for the importance of this receptor subunit in mood disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Nazario, Luiza Reali; Antonioli, Régis; Capiotti, Katiucia Marques; Hallak, Jaime Eduardo Cecílio; Zuardi, Antonio Waldo; Crippa, José Alexandre S; Bonan, Carla Denise; da Silva, Rosane Souza

    2015-08-01

    Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic-like and proconvulsant effects in mice

    DEFF Research Database (Denmark)

    Olesen, Mikkel V; Christiansen, Søren Hofman Oliveira; Gøtzsche, Casper René

    2012-01-01

    overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data...... in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene...

  5. 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.

  6. Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

    Directory of Open Access Journals (Sweden)

    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.

  7. Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice

    DEFF Research Database (Denmark)

    Refsgaard, Louise Konradsen; Pickering, Darryl S; Andreasen T., Jesper

    2017-01-01

    antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity...... test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty......-induced hypophagia test, citalopram and MK-801 showed anxiogenic-like action. All NMDAR antagonists induced hyperactivity. The high doses of ketamine and MK-801 impaired performance in the modified Y-maze test, whereas S-ketamine and RO 25-6891 showed no effects in this test. Only MK-801 impaired rotarod performance...

  8. High Resolution UHPLC-MS Metabolomics and Sedative-Anxiolytic Effects of Latua pubiflora: A Mystic Plant used by Mapuche Amerindians.

    Science.gov (United States)

    Sánchez-Montoya, Eliana L; Reyes, Marco A; Pardo, Joel; Nuñez-Alarcón, Juana; Ortiz, José G; Jorge, Juan C; Bórquez, Jorge; Mocan, Andrei; Simirgiotis, Mario J

    2017-01-01

    Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [ 3 H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1-4, 8-13, 15-18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5-7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25-27 and 30-33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids.

  9. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug Canabidiol, um componente da Cannabis sativa, como um ansiolítico

    Directory of Open Access Journals (Sweden)

    Alexandre Rafael de Mello Schier

    2012-06-01

    Full Text Available OBJECTIVES: To review and describe studies of the non-psychotomimetic constituent of Cannabis sativa, cannabidiol (CBD, as an anxiolytic drug and discuss its possible mechanisms of action. METHOD: The articles selected for the review were identified through searches in English, Portuguese, and Spanish in the electronic databases ISI Web of Knowledge, SciELO, PubMed, and PsycINFO, combining the search terms "cannabidiol and anxiolytic", "cannabidiol and anxiolytic-like", and "cannabidiol and anxiety". The reference lists of the publications included, review articles, and book chapters were handsearched for additional references. Experimental animal and human studies were included, with no time restraints. RESULTS: Studies using animal models of anxiety and involving healthy volunteers clearly suggest an anxiolytic-like effect of CBD. Moreover, CBD was shown to reduce anxiety in patients with social anxiety disorder. CONCLUSION: Future clinical trials involving patients with different anxiety disorders are warranted, especially of panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorders. The adequate therapeutic window of CBD and the precise mechanisms involved in its anxiolytic action remain to be determined.OBJETIVOS: Revisar e descrever os estudos do constituinte não psicotomimético da Cannabis sativa, o canabidiol (CBD, como ansiolítico e discutir seus possíveis mecanismos de ação. MÉTODO: Os artigos selecionados para a presente revisão foram identificados por meio de busca eletrônica em inglês, português e espanhol nos bancos de dados ISI Web of Knowledge, SciELO, PubMed e PsycINFO e combinando os termos "canabidiol e ansiolíticos", "canabidiol e semelhante ao ansiolítico" e "canabidiol e ansiedade". Foram também revisadas as listas de referências dos artigos incluídos, de revisões da literatura e de capítulos de livro. Incluímos trabalhos experimentais em humanos e em

  10. Yokukansan, a traditional Japanese herbal medicine, enhances the anxiolytic effect of fluvoxamine and reduces cortical 5-HT2A receptor expression in mice.

    Science.gov (United States)

    Ohno, Rintaro; Miyagishi, Hiroko; Tsuji, Minoru; Saito, Atsumi; Miyagawa, Kazuya; Kurokawa, Kazuhiro; Takeda, Hiroshi

    2018-04-24

    Yokukansan is a traditional Japanese herbal medicine that has been approved in Japan as a remedy for neurosis, insomnia, and irritability in children. It has also been reported to improve behavioral and psychological symptoms in patients with various forms of dementia. To evaluate the usefulness of co-treatment with an antidepressant and an herbal medicine in the psychiatric field, the current study examined the effect of yokukansan on the anxiolytic-like effect of fluvoxamine in mice. The anxiolytic-like effect in mice was estimated by the contextual fear conditioning paradigm. Contextual fear conditioning consisted of two sessions, i.e., day 1 for the conditioning session and day 2 for the test session. The expression levels of 5-HT 1A and 5-HT 2A receptor in the mouse brain regions were quantified by western blot analysis. A single administration of fluvoxamine (5-20 mg/kg, i.p.) before the test session dose-dependently and significantly suppressed freezing behavior in mice. In the combination study, a sub-effective dose of fluvoxamine (5 mg/kg, i.p.) significantly suppressed freezing behavior in mice that had been repeatedly pretreated with yokukansan (0.3 and 1 g/kg, p.o.) once a day for 6 days after the conditioning session. Western blot analysis revealed that the expression level of 5-HT 2A receptor was specifically decreased in the prefrontal cortex of mice that had been administered yokukansan and fluvoxamine. Furthermore, microinjection of the 5-HT 2A receptor antagonist ketanserin (5 nmol/mouse) into the prefrontal cortex significantly suppressed freezing behavior. The present findings indicate that repeated treatment with yokukansan synergistically enhances the anxiolytic-like effect of fluvoxamine in the contextual fear conditioning paradigm in mice in conjunction with a decrease in 5-HT 2A receptor-mediated signaling in the prefrontal cortex. Therefore, combination therapy with fluvoxamine and yokukansan may be beneficial for the treatment of

  11. Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats.

    Science.gov (United States)

    Kovács, Zsolt; D'Agostino, Dominic P; Ari, Csilla

    2018-01-01

    Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil) by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A 1 receptors (A 1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A 1 Rs may mediate such an effect, in the present study we used a specific A 1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB), as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A 1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A 1 Rs, may modulate the

  12. Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats

    Directory of Open Access Journals (Sweden)

    Zsolt Kovács

    2018-02-01

    Full Text Available Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1Rs influence the anxiolytic effect of the exogenous ketone supplement. As A1Rs may mediate such an effect, in the present study we used a specific A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine to test whether it modulates the anxiolytic effect of sub-chronically (7 days applied KSMCT in the previously tested animal model by using elevated plus maze (EPM test. We administered KSMCT (2.5 g/kg/day alone by intragastric gavage and in combination with intraperitoneally (i.p. injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg. Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day. After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB, as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1R inhibition modified (decreased the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1Rs, may modulate the

  13. Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

    Directory of Open Access Journals (Sweden)

    Fen Yang

    2017-10-01

    Full Text Available Physiologically based pharmacokinetic (PBPK/pharmacodynamic (PD models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.

  14. Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project.

    Science.gov (United States)

    Huerta, Consuelo; Abbing-Karahagopian, Victoria; Requena, Gema; Oliva, Belén; Alvarez, Yolanda; Gardarsdottir, Helga; Miret, Montserrat; Schneider, Cornelia; Gil, Miguel; Souverein, Patrick C; De Bruin, Marie L; Slattery, Jim; De Groot, Mark C H; Hesse, Ulrik; Rottenkolber, Marietta; Schmiedl, Sven; Montero, Dolores; Bate, Andrew; Ruigomez, Ana; García-Rodríguez, Luis Alberto; Johansson, Saga; de Vries, Frank; Schlienger, Raymond G; Reynolds, Robert F; Klungel, Olaf H; de Abajo, Francisco José

    2016-03-01

    Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases. Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark. Prevalence was stratified by age, sex, BZD type [(using ATC codes), i.e. BZD-anxiolytics BZD-hypnotics, BZD-related drugs and clomethiazole], indication and number of prescription. Crude prevalence rates of BZDs prescribing ranged from 570 to 1700 per 10,000 person-years over the study period. Standardization by age and sex did not substantially change the differences. Standardized prevalence rates increased in the Spanish (+13%) and UK databases (+2% and +8%) over the study period, while they decreased in the Dutch databases (-4% and -22%), the German (-12%) and Danish (-26%) database. Prevalence of anxiolytics outweighed that of hypnotics in the Spanish, Dutch and Bavarian databases, but the reverse was shown in the UK and Danish databases. Prevalence rates consistently increased with age and were two-fold higher in women than in men in all databases. A median of 18% of users received 10 or more prescriptions in 2008. Although similar methods were applied, the prevalence of BZD prescribing varied considerably across different populations. Clinical factors related to BZDs and characteristics of the databases may explain these differences. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus.

    Science.gov (United States)

    Bokor-Bratic, Marija; Cankovic, Milos; Dragnic, Natasa

    2013-10-01

    Many factors have been proposed to influence oral infection with yeast. The aim of this study was to determine the prevalence of oral yeasts in oral lichen planus (OLP) patients and control subjects, and to perform a multiple logistic regression analysis to identify factors that influence oral Candida infection in OLP patients. In this cross-sectional study, 90 new patients with OLP and 90 sex- and age-matched control subjects with no mucosal lesions were interviewed about their health status, use of medication, and smoking and alcohol habits. Swab and unstimulated whole saliva samples were collected and salivary pH was measured. A positive Candida culture was more prevalent among OLP patients (48.9%) than among control subjects (26.7%). Candida albicans was the most frequently isolated species in both groups. By logistic regression analysis, unstimulated whole salivary flow rates of 0.11-0.24 ml min(-1) (OR = 5.90) and 0.25-0.32 ml min(-1) (OR = 3.51) and benzodiazepine anxiolytics intake (OR = 8.30) were independently associated with the presence of Candida among OLP patients. Age, denture wearing, levels of dentition, decreased salivary pH, antihypertensive drugs, and alcohol consumption were not associated with oral Candida infection in OLP patients. The results indicate that data on benzodiazepine anxiolytics intake and evaluation of unstimulated whole salivary flow rate should be considered as part of the clinical evaluation to identify OLP patients at risk for Candida infection. © 2013 Eur J Oral Sci.

  16. 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.

  17. AVCRI104P3, a novel multitarget compound with cognition-enhancing and anxiolytic activities: studies in cognitively poor middle-aged mice.

    Science.gov (United States)

    Giménez-Llort, L; Ratia, M; Pérez, B; Camps, P; Muñoz-Torrero, D; Badia, A; Clos, M V

    2015-06-01

    The present work describes, for the first time, the in vivo effects of the multitarget compound AVCRI104P3, a new anticholinesterasic drug with potent inhibitory effects on human AChE, human BuChE and BACE-1 activities as well as on the AChE-induced and self-induced Aβ aggregation. We characterized the behavioral effects of chronic treatment with AVCRI104P3 (0.6 μmol kg(-1), i.p., 21 days) in a sample of middle aged (12-month-old) male 129/Sv×C57BL/6 mice with poor cognitive performance, as shown by the slow acquisition curves of saline-treated animals. Besides, a comparative assessment of cognitive and non-cognitive actions was done using its in vitro equipotent doses of huprine X (0.12 μmol kg(-1)), a huperzine A-tacrine hybrid. The screening assessed locomotor activity, anxiety-like behaviors, cognitive function and side effects. The results on the 'acquisition' of spatial learning and memory show that AVCRI104P3 exerted pro-cognitive effects improving both short- and long-term processes, resulting in a fast and efficient acquisition of the place task in the Morris water maze. On the other hand, a removal test and a perceptual visual learning task indicated that both AChEIs improved short-term 'memory' as compared to saline treated mice. Both drugs elicited the same response in the corner test, but only AVCRI104P3 exhibited anxiolytic-like actions in the dark/light box test. These cognitive-enhancement and anxiolytic-like effects demostrated herein using a sample of middle-aged animals and the lack of adverse effects, strongly encourage further studies on AVCRI104P3 as a promising multitarget therapeutic agent for the treatment of cholinergic dysfunction underlying natural aging and/or dementias. Copyright © 2015. Published by Elsevier B.V.

  18. 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

  19. 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.

  20. Anxiolytic-Like Effects and Increase in Locomotor Activity Induced by Infusions of NMDA into the Ventral Hippocampus in Rat: Interaction with GABAergic System.

    Science.gov (United States)

    Bina, Payvand; Rezvanfard, Mehrnaz; Ahmadi, Shamseddin; Zarrindast, Mohammad Reza

    2014-10-01

    In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABAA system on anxiety-like behaviors. We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 μg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 μg/rat) or bicuculline (0.5 and 1 μg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 μg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 μg/rat) along with low doses of NMDA (0.0625 and 0.125 μg/rat) showed a tendency to increase %OAT, %OAE and locomotor activity; however, no interaction was observed between the drugs. Interestingly, intra-VH co-infusions of bicuculline (0.5 μg/rat) along with effective doses of NMDA (0.25 and 0.5 μg/rat) decreased %OAT, %OAE and locomotor activity, and a significant interaction between two drugs was observed. It can be concluded that GABAergic system may mediate the anxiolytic-like effects and increase in locomotor activity induced by NMDA in the VH.

  1. Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil.

    Science.gov (United States)

    Rabbani, Mohammed; Sajjadi, Seyed Ebrahim; Vaezi, Arefeh

    2015-01-01

    Ocimum basilicum belongs to Lamiaceae family and has been used for the treatment of wide range of diseases in traditional medicine in Iranian folk medicine. Due to the progressive need to anti-anxiety medications and because of the similarity between O. basilicum and Salvia officinalis, which has anti-anxiety effects, we decided to investigate the anxiolytic and sedative activity of hydroalcoholic extract and essential oil of O. basilicum in mice by utilizing an elevated plus maze and locomotor activity meter. The chemical composition of the plant essential oil was also determined. The essential oil and hydroalcoholic extract of this plant were administered intraperitoneally to male Syrian mice at various doses (100, 150 and 200 mg/kg of hydroalcoholic extract and 200 mg/kg of essential oil) 30 min before starting the experiment. The amount of hydroalcoholic extract was 18.6% w/w and the essential oil was 0.34% v/w. The major components of the essential oil were methyl chavicol (42.8%), geranial (13.0%), neral (12.2%) and β-caryophyllene (7.2%). HE at 150 and 200 mg/kg and EO at 200 mg/kg significantly increased the time passed in open arms in comparison to control group. This finding was not significant for the dose of 100 mg/kg of the extract. None of the dosages had significant effect on the number of entrance to the open arms. Moreover, both the hydroalcoholic extract and the essential oil decreased the locomotion of mice in comparison to the control group. This study shows the anxiolytic and sedative effect of hydroalcoholic extract and essential oil of O. basilicum. The anti-anxiety and sedative effect of essential oil was higher than the hydroalcoholic extract with the same doses. These effects could be due to the phenol components of O. basilicum.

  2. Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of antidepressant and anxiolytic drugs in neonatal meconium and maternal hair.

    Science.gov (United States)

    Pichini, Simona; Cortes, Laura; Marchei, Emilia; Solimini, Renata; Pacifici, Roberta; Gomez-Roig, Mª Dolores; García-Algar, Oscar

    2016-01-25

    A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of 22 antidepressant and anxiolytic drugs ad metabolites in the three consecutive maternal hair segments representing the pregnancy trimesters and paired neonatal meconium samples. After hair washing with methyl alcohol and diethyl ether and subsequent addition of internal standards, hair samples were treated with 500 μl VMA-T M3 reagent for 1h at 100 °C. After cooling, 100 μl M3 extract were diluted with 400 μl water and a volume of 10 μl was injected into chromatographic system. Meconium samples were firstly treated with 1 ml methyl alcohol and the organic layer back-extracted twice with 1.5 ml of a mixture of ethylacetate:hexane (80:20, v/v). Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.05-1 ng/mg hair and 5-25 ng/g meconium depending on analyte under investigation;) to 10 ng/mg hair and 1000 ng/g meconium, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 66.6% and 95.3%, depending on the considered analyte and biological matrix. Using the validated method, 7 mothers were found positive to one or more hair segments and 5 meconium samples were found positive to one or more antidepressant and anxiolytic drugs, assessing prenatal exposure to these drugs following maternal consumption in one or more pregnancy trimesters. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Room-temperature super-extraction system (RTSES optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice

    Directory of Open Access Journals (Sweden)

    Yin Shih-Hsi

    2012-11-01

    Full Text Available Abstract Background Xiao-Yao-San (XYS is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES to extract the major active components of XYS and enhance their psycho-pharmacological effects. Methods The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro and a depression-like C57BL/6 J mouse model (in vivo. The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM test and the antidepressant effects were evaluated by the forced swimming test (FST and tail suspension test (TST. Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting. Results XYS/RTSES (300 μg/mL diminished reserpine-induced glial cell death more effectively than either XYS (300 μg/mL or fluoxetine (30 μM at 24 h (P = 0.0481 and P = 0.054, respectively. Oral administration of XYS/RTSES (500 mg/kg/day for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177 and shuttle activity (P = 0.00149 on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538 and FST (P = 0.0000053839. XYS/RTSES also improved the regulation of blood glucose (P = 0.0305 and increased the insulin sensitivity (P = 0.0093. The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions. Conclusion The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

  4. Juvenile polyposis of the stomach--a novel cause of hypergastrinemia

    DEFF Research Database (Denmark)

    Papay, Karen D; Falck, Vincent G; Poulsen, Steen Seier

    2010-01-01

    A 38-year-old female presented with a 3-year history of postprandial abdominal pain, refractory nausea, vomiting and hematemesis. She appeared malnourished and her symptoms were refractory to previous treatment with acid-suppressive drugs, prokinetics and antiemetics. Her medical history was sign...

  5. Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6J and BALB/c mice injected with GABA- and 5HT-anxiolytic agents.

    Science.gov (United States)

    Lalonde, Robert; Strazielle, Catherine

    2010-06-01

    Two 5HT(1A) receptor agonists and chlordiazepoxide were examined in open-field, elevated plus maze, and emergence tests. At doses with no effect in the open-field, chlordiazepoxide increased open and open/total arm visits as well as open arm duration in the elevated plus maze, whereas 5HT(1A) receptor agonists showed an anxiolytic response on a single measure. The anxiolytic action of chlordiazepoxide was limited to the less active BALB/c strain. Unlike the 5HT(1A) receptor agonists, chlordiazepoxide was also anxiolytic in the emergence test, once again only in BALB/c and not C57BL/6J mice. Significant correlations were found between emergence latencies and specific indicators of anxiety in the elevated plus-maze in chlordiazepoxide-treated but not in mice treated with buspirone and 8-OH-DPAT. These results indicate that elevated plus-maze and emergence tests depend on benzodiazepine receptors. In contrast, 5HT(1A) receptor agonists were ineffective in the emergence test and no correlation was found between emergence latencies and specific indicators of anxiety in the elevated plus-maze. Though superficially similar, the emergence test seems to tap into a partially separate facet of anxiety.

  6. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years.

    Science.gov (United States)

    Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Riba, Jordi; Zuardi, Antônio W; Hallak, Jaime E C

    2016-06-01

    To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.

  7. The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats.

    Science.gov (United States)

    Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

    2016-03-01

    Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain, and its abnormalities have been linked to schizophrenia. The present study was designed to investigate the ability of the NO donor sodium nitroprusside (SNP) to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. The ability of SNP to reverse ketamine-induced memory deficits and social withdrawal were assessed using the novel object recognition task (NORT) and the social interaction test, respectively. Furthermore, since anxiety disorders are noted to occur commonly in schizophrenics, the effects of SNP on anxiety-like behaviour were examined using the light/dark test. Locomotor activity was also assessed as an independent measure of the potential motoric effects of this NO donor. SNP (0.3 and 1 mg/kg) reversed ketamine (3 mg/kg)-induced short-term recognition memory deficits. SNP (1 mg/kg) counteracted the ketamine (8 mg/kg)-induced social isolation in the social interaction test. The anxiolytic-like effects in the light/dark test of SNP (1 mg/kg) cannot be attributed to changes in locomotor activity. Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia-like behavioural deficits. The data also suggest a role of NO in anxiety.

  8. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years

    Science.gov (United States)

    dos Santos, Rafael G.; Osório, Flávia L.; Crippa, José Alexandre S.; Riba, Jordi; Zuardi, Antônio W.; Hallak, Jaime E. C.

    2016-01-01

    To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings. PMID:27354908

  9. Evaluation of Anticonvulsant, Sedative, Anxiolytic, and Phytochemical Profile of the Methanol Extract from the Aerial Parts of Swertia corymbosa (Griseb. Wight ex C.B. Clarke

    Directory of Open Access Journals (Sweden)

    G. Mahendran

    2014-01-01

    Full Text Available The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH. After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg (P<0.01, P<0.001 increased the number of rearings. However, the number of central motor and ambulation (P<0.01, P<0.001 were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P<0.001 in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125–500 mg/kg protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P<0.01 and P<0.001 dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.

  10. Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats.

    Science.gov (United States)

    Violle, Nicolas; Rozan, Pascale; Demais, Hervé; Nyvall Collen, Pi; Bisson, Jean-François

    2018-05-01

    The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans. After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST). In the FST, MSP effects were compared to the reference antidepressant drug imipramine (IMI) (10 mg/kg/day). Acute and sub-chronic toxicities of the extract were also assessed in male and female rats following OECD guidelines. MSP treatment did not modify anxiety-related behaviour in the EPM. In contrast, MSP induced a dose-dependent reduction of immobility behaviour in the FST. At the highest tested dose of 40 mg/kg, MSP displayed a significant antidepressant-like effect similar to IMI. MSP did not modify the exploratory behaviour of rats in the open field test and did not produce any toxic effect. MSP may potentially represent a good adjunct or alternative to existing antidepressant therapeutics. Further studies are necessary to confirm the mechanism of action of MSP and its modulation of brain functioning.

  11. 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.

  12. Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

    International Nuclear Information System (INIS)

    Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

    2015-01-01

    The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT 3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV

  13. Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

    Science.gov (United States)

    Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

    2015-03-01

    The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

    Science.gov (United States)

    Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D; Peterson, Veronica L; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-10-01

    The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. Copyright © 2017 Society of Biological Psychiatry. Published by

  15. Determination of alpidem, an imidazopyridine anxiolytic, and its metabolites by column-switching high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Flaminio, L; Ripamonti, M; Ascalone, V

    1994-05-13

    Alpidem, 6-chloro-2-(4-chlorophenyl)-N,N-dipropylimidazo[1,2-a]pyridine- 3-acetamide, is an anxiolytic imidazopyridine that undergoes a first-pass elimination after oral administration to humans; it is actively metabolized and three circulating metabolites have been identified in plasma due to N-dealkylation, oxidation or a combination of both processes. For the determination of the unchanged drug and its metabolites in human plasma, a column-switching HPLC method was developed. The method, based on solid-phase extraction (performed on-line), involves the automatic injection of plasma samples (200 microliters) on to a precolumn filled with C18 material, clean-up of the sample with water in order to remove protein and salts and transfer of the analytes to the analytical column (after valve switching) by means of the mobile phase. All the processes were performed in the presence of an internal standard, a compound chemically related to alpidem. During the analytical chromatography, the precolumn was flushed with different solvents and after regeneration with water, it was ready for further injections. The analytical column was a C8 type and the mobile phase was acetonitrile-methanol-phosphate buffer solution (45:15:45, v/v/v) at a flow-rate of 1.5 ml min-1. The column was connected to a fluorimetric detector operating at excitation and emission wavelengths of 255 and 423 nm, respectively. The limits of quantitation of alpidem and three metabolites were 2.5 and 1.5 ng ml-1, respectively, in human plasma.

  16. Dorsal hippocampal microinjection of chlorpheniramine reverses the anxiolytic-like effects of l-histidine and impairs emotional memory in mice.

    Science.gov (United States)

    Canto-de-Souza, L; Garção, D C; Romaguera, F; Mattioli, R

    2015-02-05

    Several findings have pointed to the role of histaminergic neurotransmission in the modulation of anxiety-like behaviors and emotional memory. The elevated plus-maze (EPM) test has been widely used to investigate the process of anxiety and also has been used to investigate the process of learning and memory. Visual cues are relevant to the formation of spatial maps, and as the hippocampus is involved in this task, experiment 1 explored this issue. Experiment 2 investigated the effects of intraperitoneal (i.p.) injections of l-histidine (LH, a precursor of histamine) and of intra-dorsal hippocampus (intra-DH) injections of chlorpheniramine (CPA, an H1 receptor antagonist) on anxiety and emotional memory in mice re-exposed to the EPM. Mice received saline (SAL) or LH i.p. and SAL or CPA (0.016, 0.052, and 0.16 nmol/0.1 μl) intra-DH prior to Trial 1 (T1) and Trial 2 (T2). No significant changes were observed in the number of enclosed-arm entries (EAE) in T1, an EPM index of general exploratory activity. LH had an anxiolytic-like effect that was reversed by intra-DH injections of CPA. T2 versus T1 analysis revealed that only the lower dose of CPA resulted in impaired emotional memory. Combined injections of LH and CPA revealed that higher doses of CPA impair emotional memory. Taken together, these results suggest that LH and H1 receptors present in the dorsal hippocampus are involved in anxiety-related behaviors and emotional memory in mice submitted to EPM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Reprint of "Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)".

    Science.gov (United States)

    Nazario, Luiza Reali; Antonioli, Régis Junior; Capiotti, Katiucia Marques; Hallak, Jaime Eduardo Cecílio; Zuardi, Antonio Waldo; Crippa, José Alexandre S; Bonan, Carla Denise; da Silva, Rosane Souza

    2015-12-01

    Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine. Copyright © 2015. Published by Elsevier Inc.

  18. Enhanced Patient Expectant and Antiemetic Drug Efficacy

    National Research Council Canada - National Science Library

    Roscoe, Joseph

    1999-01-01

    ...; and writing abstracts, papers, and book chapters. The training also includes the design, implementation and analyses of a randomized controlled experiment examining the relationship between cancer patient expectations for experiencing chemotherapy...

  19. tic antiemetic in patients receiving intrathec

    African Journals Online (AJOL)

    2014-06-02

    Jun 2, 2014 ... Lagos State School of Anaesthesia, Badagry, Nigeria. 3. Obafemi Awolowo University I le-Ife, Nigeria. 4. ... a large proportion of surgical procedures are amenable to regional anesthesia, thus increasing its ..... women undergoing ambulatory laparoscopic surgery. Br J Anaesth 2000;84: 459 – 462. 14.

  20. Investigation of the laxative, spasmolytic and prokinetic properties of ...

    African Journals Online (AJOL)

    It is also used for the management of constipation, skin disorders, ... provided unrestricted access to balanced diet. (Hi-Tech Feeds Pvt. Ltd. ... Resources, Commission on Life Sciences [8]. Approval ..... Decreased physical activity, depressed mood, piloerection ... The authors declare that this work was done by the authors ...

  1. Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs): a methodological approach to assess consistencies across databases from the PROTECT-EU project.

    Science.gov (United States)

    Requena, Gema; Huerta, Consuelo; Gardarsdottir, Helga; Logie, John; González-González, Rocío; Abbing-Karahagopian, Victoria; Miret, Montserrat; Schneider, Cornelia; Souverein, Patrick C; Webb, Dave; Afonso, Ana; Boudiaf, Nada; Martin, Elisa; Oliva, Belén; Alvarez, Arturo; De Groot, Mark C H; Bate, Andrew; Johansson, Saga; Schlienger, Raymond; Reynolds, Robert; Klungel, Olaf H; de Abajo, Francisco J

    2016-03-01

    Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

  2. The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

    Directory of Open Access Journals (Sweden)

    Luisa Ponzoni

    2017-08-01

    Full Text Available 3,4-Methylenedioxymethamphetamine (MDMA and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB and para-methoxyamphetamine (PMA, are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg, DOB (0.5 mg/kg, or PMA (0.005, 0.1, or 0.25 mg/kg were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg, before carrying out conditioned place preference (CPP, social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1 rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2 prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3 anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish after treatment with the most active doses of MDMA (10 mg/kg, DOB (0.5 mg/kg, and PMA (0.1 mg/kg as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance

  3. Second meeting of the French CEIP (Centres d'Evaluation et d'Information sur la Pharmacodépendance). Part I: how to evaluate and prevent the abuse and dependence on hypnotic/anxiolytic drugs?

    Science.gov (United States)

    Micallef-Roll, Joëlle; Lapeyre-Mestre, Maryse

    2009-01-01

    The second meeting of the French CEIP (Centres d'Evaluation et d'Information sur la Pharmacodépendance) was organized during the annual congress of the French Society of Pharmacology Therapeutics and Physiology in 2008. The aim of this meeting was to update the knowledge on abuse and dependence of the anxiolytics and hypnotics from different points of view (pharmacoepidemiology, epidemiology and treatment). The first part of this meeting summarized the pharmacological data obtained by the pharmacoepidemiological tools developed by the CEIP network. Even if the abuse liability of these agents is not a new problem, it remains always present and characterized by differences of misuse between drugs in real-life settings. The second part targeted to a subtype of consumers, the elderly population, because older patients are more likely to be prescribed with multiple prescriptions and also more at risk for prescription abuse. Despite this evidence, there is a scarcity of information on the factors associated with a such behaviour and its screening, assessment, diagnosis and treatment.

  4. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP tests. Additionally, compared with the chronic alcohol (1.0% treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5% generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  5. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Science.gov (United States)

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  6. Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies.

    Science.gov (United States)

    Ferlemi, Anastasia-Varvara; Katsikoudi, Antigoni; Kontogianni, Vassiliki G; Kellici, Tahsin F; Iatrou, Grigoris; Lamari, Fotini N; Tzakos, Andreas G; Margarity, Marigoula

    2015-07-25

    Our aim was to investigate the possible effects of regular drinking of Rosmarinus officinalis L. leaf infusion on behavior and on AChE activity of mice. Rosemary tea (2% w/w) phytochemical profile was investigated through LC/DAD/ESI-MS(n). Adult male mice were randomly divided into two groups: "Rosemary-treated" that received orally the rosemary tea for 4weeks and "control" that received drinking water. The effects of regular drinking of rosemary tea on behavioral parameters were assessed by passive avoidance, elevated plus maze and forced swimming tests. Moreover, its effects on cerebral and liver cholinesterase (ChE) isoforms activity were examined colorimetricaly. Phytochemical analysis revealed the presence of diterpenes, flavonoids and hydroxycinnamic derivatives in rosemary tea; the major compounds were quantitatively determined. Its consumption rigorously affected anxiety/fear and depression-like behavior of mice, though memory/learning was unaffected. ChE isoforms activity was significantly decreased in brain and liver of "rosemary treated" mice. In order to explain the tissue ChE inhibition, principal component analysis, pharmacophore alignment and molecular docking were used to explore a possible relationship between main identified compounds of rosemary tea, i.e. rosmarinic acid, luteolin-7-O-glucuronide, caffeic acid and known AChE inhibitors. Results revealed potential common pharmacophores of the phenolic components with the inhibitors. Our findings suggest that rosemary tea administration exerts anxiolytic and antidepressant effects on mice and inhibits ChE activity; its main phytochemicals may function in a similar way as inhibitors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. The Anxiolytic Properties of Vernonia Amygdalina

    African Journals Online (AJOL)

    Dr Olaleye

    itself in form of phobia, panic attacks, post‐traumatic stress disorder, social anxiety disorder or generalized anxiety disorder. Moreover ... MATERIALS AND METHODS. Plant preparation ... like behavior in laboratory animals. The apparatus is.

  8. 21 CFR 336.50 - Labeling of antiemetic drug products.

    Science.gov (United States)

    2010-04-01

    ... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... under 12 years of age. “Do not give this product to children who have a breathing problem such as...

  9. Dexamethasone enhances the anti-emetic effect of metoclopramide ...

    African Journals Online (AJOL)

    Ninety patients, ASA I or II, aged 21-64years were randomly selected to either the dexamethasone-metoclopramide group, metoclopramide group or dexamethasone group using computer-generated random numbers . Spinal anaesthesia was induced in the sitting position under strict aseptic technique with hyperbaric ...

  10. Antiemetic Medicines: OTC Relief for Nausea and Vomiting

    Science.gov (United States)

    ... CorrectlyPain Relievers: Understanding Your OTC OptionsAntacids and Acid Reducers: OTC Relief for Heartburn and Acid RefluxOTC Cough ... Loss and Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics ...

  11. Antiemetic prophylaxis with promethazine or ondansetron in major ...

    African Journals Online (AJOL)

    Southern African Journal of Anaesthesia and Analgesia ... Abstract. Background: Postoperative nausea and vomiting remain a significant cause of morbidity among patients undergoing general anaesthesia. ... Drowsiness was a significant side-effect with promethazine, and this will be a disadvantage in ambulatory surgery.

  12. Profilaxia antiemética em cirurgia de abdome agudo: estudo comparativo entre droperidol, metoclopramida, tropisetron, granisetron e dexametasona Profilaxis antiemética en cirugía de abdomen agudo: estudio comparativo entre droperidol, metoclopramida, tropisetrón, granisetrón y dexametasona Prophylactic antiemetic therapy for acute abdominal surgery: a comparative study of droperidol, metoclopramide, tropisetron, granisetron and dexamethasone

    Directory of Open Access Journals (Sweden)

    Víctor Contreras-Domínguez

    2008-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A incidência de náuseas e vômitos pós-operatórios (NVPO gira em torno de 30%. A profilaxia de NVPO foi objeto de múltiplos estudos, tanto para tentar diminuir esse problema como para comparar o índice custo-benefício do tratamento utilizado. Esse estudo comparou a eficácia de cinco fármacos antieméticos em apendicectomia. MÉTODO: Estudo clínico prospectivo controlado, duplamente encoberto de 150 pacientes ASA I e II com IMC JUSTIFICATIVA Y OBJETIVOS: La incidencia de náuseas y vómitos peri operatorios (NVPO se estima en un 30%. La profilaxis de NVPO ha sido objetivo de múltiples estudios, tanto para intentar disminuir este problema como a su vez comparar índice costo-beneficio de la terapia utilizada. Este estudio evalúa la utilización de 5 fármacos antieméticos en relación a grupo control para apendicectomía de urgencia. MÉTODO: Estudio clínico prospectivo controlado, doble ciego de 150 pacientes ASA I y II con IMC BACKGROUND AND OBJECTIVES: It is calculated that the incidence of postoperative nausea and vomiting (PONV is approximately 30%. The prophylaxis of PONV has been the subject of several studies, both to decrease this problem and to compare the cost-benefit ration of the treatment used. The objective of this study was to compare the efficacy of 5 antiemetic drugs with a control group in emergency appendectomy. METHODS: A controlled, double-blind, prospective study with 150 patients, ASA I and II, BMI < 30, undergoing appendectomy, was undertaken. Patients were divided in six groups: Group 1 (n = 25: 5 mL of normal saline; Group 2 (n = 25: 0.625 mg of droperidol; Group 3 (n = 25: 20 mg of metoclopramide; Group 4 (n = 25: 5 mg of tropisetron; Group 5 (n = 25: 1 mg of granisetron; Group 6 (n = 25: 4 mg of dexamethasone. Monitoring included ECG, non-invasive blood pressure, O2 saturation, P ET CO2, anesthetic gas analyzer and peripheral nerve stimulator. The presence of PONV, complications

  13. Prokinetic and laxative effects of Xiao'er Qixingcha, a household ...

    African Journals Online (AJOL)

    Materials and Methods: In the in vivo study, small intestinal transit rates and fecal output characters (fecal number and fecal weight) were measured on normal and two models of constipated mice (induced by diphenoxylate and by water-fasting respectively). In the in vivo study, the contraction rates of ileum smooth muscle ...

  14. A radioimmunoassay method for the novel gastrointestinal prokinetic agent, renzapride, in plasma

    International Nuclear Information System (INIS)

    Al-Azawie, D.M.; Webb, A.J.; Kelly, H.C.; Davies, B.E.

    1990-01-01

    Renzapride, BRL 24924 {4-amino-5-chloro-2- methoxy-N[4-(1-azabicyclo- [3,3,1] nonyl) benzamide]} is a novel compound that enhances gut motility without causing CNS dopamine block or prolactin release. It is being processed as a potential stimulant of upper gut motility and gastric emptying. Until now the only available method used to determine the concentrations of renzapride during clinical studies was a reversed phase h.p.l.c. assay (Kelly and Davies, 1988). Although the h.p.l.c. assay was used to determine renzapride in urine, the technique lacked the sensitivity required to quantify the low concentrations of the drug in plasma. The authors describe the development of a sensitive, specific, and simple radioimmunoassay method that can be used to determine renzapride concentrations in human plasma following therapeutic doses. (author)

  15. Evaluation of new gastro-intestinal prokinetic (ENGIP-I) study.

    Science.gov (United States)

    Walwaikar, Pradeep P; Kulkarni, Sujay S; Bargaje, Rahul S

    2005-10-01

    The ENGIP-I study was conducted to investigate the efficacy, and safety of itopride in patients of gastro-oesophageal reflux disease. There were significant reductions in heartburn frequency, heartburn severity, gastro-oesophageal regurgitation frequency at day 3 only. ENGIP-I study concluded that itopride was well tolerated by patients and appears to be the drug of choice in patients with gastro-oesophageal reflux disease.

  16. Pharmacotherapy of stomach diseases in dogs

    Directory of Open Access Journals (Sweden)

    Trailović Saša M.

    2005-01-01

    Full Text Available Stomach diseases have an important place in the clinical pathology of dogs. Etiological factors can be nutritive, chemical, or infective, but treatment implies certain common general principles and a certain number of therapy protocols which are most often used. On the other hand, a part of the medicines used in the pharmacotherapy of stomach diseases in dogs are taken from the palette of medicines intended for human use, so that a regular dosage and regime of implementation are the main precondition for the success of the applied therapy. Drugs used in the treatment of stomach diseases include antiemetics, prokinetics, antacids, mucoprotectives, anticholinergics, H2-antagonists, proton pump inhibitors, semisynthetic derivatives of prostaglandin E1, and others. The therapy of stomach diseases implies the simultaneous application of several drugs from different pharmacodynamic groups (for instance, an antiemetic, a prokinetic, an antacid, and an Hg antagonist or a proton pump inhibitor when it is necessary to establish a correct regime of implementation because of possible interaction, which will also be discussed in this work.

  17. Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor.

    Science.gov (United States)

    Chaki, Shigeyuki; Hirota, Shiho; Funakoshi, Takeo; Suzuki, Yoshiko; Suetake, Sayoko; Okubo, Taketoshi; Ishii, Takaaki; Nakazato, Atsuro; Okuyama, Shigeru

    2003-02-01

    We investigated the effects of a novel melanocortin-4 (MC4) receptor antagonist,1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine (MCL0129) on anxiety and depression in various rodent models. MCL0129 inhibited [(125)I][Nle(4)-D-Phe(7)]-alpha-melanocyte-stimulating hormone (alpha-MSH) binding to MC4 receptor with a K(i) value of 7.9 nM, without showing affinity for MC1 and MC3 receptors. MCL0129 at 1 microM had no apparent affinity for other receptors, transporters, and ion channels related to anxiety and depression except for a moderate affinity for the sigma(1) receptor, serotonin transporter, and alpha(1)-adrenoceptor, which means that MCL0129 is selective for the MC4 receptor. MCL0129 attenuated the alpha-MSH-increased cAMP formation in COS-1 cells expressing the MC4 receptor, whereas MCL0129 did not affect basal cAMP levels, thereby indicating that MCL0129 acts as an antagonist at the MC4 receptor. Swim stress markedly induced anxiogenic-like effects in both the light/dark exploration task in mice and the elevated plus-maze task in rats, and MCL0129 reversed the stress-induced anxiogenic-like effects. Under nonstress conditions, MCL0129 prolonged time spent in the light area in the light/dark exploration task and suppressed marble-burying behavior. MCL0129 shortened immobility time in the forced swim test and reduced the number of escape failures in inescapable shocks in the learned helplessness test, thus indicating an antidepressant potential. In contrast, MCL0129 had negligible effects on spontaneous locomotor activity, Rotarod performance, and hexobarbital-induced anesthesia. These observations indicate that MCL0129 is a potent and selective MC4 antagonist with anxiolytic- and antidepressant-like activities in various rodent models. MC4 receptor antagonists may prove effective for treating subjects with stress-related disorders such as depression and/or anxiety.

  18. Anticonvulsant and Anxiolytic Properties of the Roots of Grewia ...

    African Journals Online (AJOL)

    Materials and Methods: The ethanolic extract of the root of G. bicolourat (200, 400 and 800 mg/kg, i.p was studied for its anticonvulsant effect on four in vivo rat models (Maximal Electroshock Seizure (MES), Pentylenetetrazole (PTZ)-, picrotoxin (PIC)- and Strychnine (STR) - induced seizures). Simple activity meter was used ...

  19. Anxiolytic Effect of Aromatherapy Massage in Patients with Breast Cancer

    OpenAIRE

    Imanishi, Jiro; Kuriyama, Hiroko; Shigemori, Ichiro; Watanabe, Satoko; Aihara, Yuka; Kita, Masakazu; Sawai, Kiyoshi; Nakajima, Hiroo; Yoshida, Noriko; Kunisawa, Masahiro; Kawase, Masanori; Fukui, Kenji

    2009-01-01

    We examined how aromatherapy massage influenced psychologic and immunologic parameters in 12 breast cancer patients in an open semi-comparative trial. We compared the results 1 month before aromatherapy massage as a waiting control period with those during aromatherapy massage treatment and 1 month after the completion of aromatherapy sessions. The patients received a 30 min aromatherapy massage twice a week for 4 weeks (eight times in total). The results showed that anxiety was reduced in on...

  20. Evaluation of Lorazepam as an Anxiolytic Agent in Psychiatric Practice

    African Journals Online (AJOL)

    ... in a study involving 35 non-hospitalised patients. No serious sideeffects were encountered and the drug, administered orally, was well tolerated. The patients exhibited anxiety as a primary symptom or in association with other disease entities. The drug appeared to be most effective against insomnia, tension and anxiety.

  1. Evaluation of Lorazepam as an Anxiolytic Agent in Psychiatric Practice

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... schizophrenia (Table I). Excluded from the study were patients with known hypersensitivity to the test drug, or with serious debiJitating organic disease, and pregnant women. Generally lorazepam is not indicated in schizo- phrenic patients, but in 2 schizophrenic patients in this series the symptoms were of ...

  2. The pharmacology of TD-8954, a potent and selective 5-HT4 receptor agonist with gastrointestinal prokinetic properties

    Directory of Open Access Journals (Sweden)

    David T Beattie

    2011-05-01

    Full Text Available This study evaluated the in vitro and in vivo pharmacological properties of TD-8954, a potent and selective 5-HT4 receptor agonist. TD-8954 had high affinity (pKi = 9.4 for human recombinant 5-HT4(c (h5-HT4(c receptors, and selectivity (> 2,000-fold over all other 5-HT receptors and non-5-HT receptors, ion channels, enzymes and transporters tested (n = 78. TD-8954 produced an elevation of cAMP in HEK-293 cells expressing the h5-HT4(c receptor (pEC50 = 9.3, and contracted the guinea pig colonic longitudinal muscle/myenteric plexus (LMMP preparation (pEC50 = 8.6. TD-8954 had moderate intrinsic activity (IA in the in vitro assays. In conscious guinea pigs, subcutaneous (s.c. administration of TD 8954 (0.03 - 3 mg/kg increased the colonic transit of carmine red dye, reducing the time taken for its excretion. Following intraduodenal (i.d. dosing to anesthetized rats, TD 8954 (0.03 - 10 mg/kg evoked a dose-dependent relaxation of the esophagus. Following oral administration to conscious dogs, TD 8954 (10 and 30 µg/kg produced an increase in contractility of the antrum, duodenum and jejunum. In a single ascending oral dose study in healthy human subjects, TD-8954 (0.1 - 20 mg increased bowel movement frequency and reduced the time to first stool. It is concluded that TD-8954 is a potent and selective 5-HT4 receptor agonist in vitro, with robust in vivo stimulatory activity in the gastrointestinal (GI tract of guinea pigs, rats, dogs and humans. TD-8954 may have clinical utility in patients with disorders of reduced GI motility.

  3. Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.

    Science.gov (United States)

    Chiba, Toshimi; Tokunaga, Yumi; Ikeda, Keisei; Takagi, Ryo; Chishima, Raita; Terui, Torahiko; Kudara, Norihiko; Endo, Masaki; Inomata, Masaaki; Orii, Seishi; Suzuki, Kazuyuki

    2007-09-01

    The effect of itopride hydrochloride or ranitidine on the health-related quality of life (HRQoL) of functional dyspepsia is not well known. Our aim was to assess the HRQoL before and after administration of itopride hydrochloride or ranitidine in patients with functional dyspepsia. A total of 18 functional dyspepsia patients (12 women, 6 men; mean age 52.5 y.o.) were enrolled. We determined the HRQoL using two different inquiry systems: the 36 item short form of the Medical Outcome Study Questionnaire (SF-36) and the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined before administration of drug, and two, four, and eight weeks after administration of drug. After administration of itopride hydrochloride, the SF-36 mental health scale and GSRS indigestion syndrome score and constipation syndrome score were significantly improved compared to before administration (p Itopride hydrochloride would be useful for the treatment of dysmotility-type functional dyspepsia, whereas ranitidine would be beneficial for ulcer-type functional dyspepsia.

  4. Rat duodenal motility in vitro: Prokinetic effects of DL-homocysteine thiolactone and modulation of nitric oxide mediated inhibition

    Directory of Open Access Journals (Sweden)

    Stojanović Marija

    2013-01-01

    Full Text Available Homocysteine is a significant but modifiable risk factor for vascular diseases. As gastrointestinal smooth musculature is similar to blood vessel muscles, we investigated how elevated homocysteine levels affect nitric oxide-mediated neurotransmission in the gut. There is accumulated evidence that a dysfunction of NO neurons in the myenteric plexus may cause various diseases in the gastrointestinal tract such as achalasia, diabetic gastroparesis and infantile hypertrophic pyloric stenosis. In the present study, we aimed to assess the effects of homocysteine on NO-mediated responses in vitro, and to examine the effects of DL-homocysteine thiolactone on the spontaneous motility of rat duodenum and nitrergic neurotransmission. DL-homocysteine thiolactone concentration of 10 μmol/L leads to the immediate increase in tone, amplitude and frequency of spontaneous movements in isolated rat duodenum. L-NAME (30 μmol/L leads to an increase in basal tone, amplitude and frequency of spontaneous contractions. The relaxations induced by EFS were significantly reduced in duodenal segments incubated in DL-homocysteine thiolactone compared with the control group. EFS-induced relaxations were inhibited by L-NAME in both experimental and control groups. These results suggest that a high level of homocysteine causes an important impairment of non-adrenergic non-cholinergic innervation of the rat duodenum. [Projekat Ministarstva nauke Republike Srbije, br. 175043

  5. Antiemetic and Myeloprotective Effects of Rhus verniciflua Stoke in a Cisplatin-Induced Rat Model

    Directory of Open Access Journals (Sweden)

    Hyo-Seon Kim

    2017-01-01

    Full Text Available Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis but reduced the normal diet intake (anorexia whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1β, revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.

  6. Determination of metal ion contents of two antiemetic clays use in Geophagy

    Directory of Open Access Journals (Sweden)

    Solomon E. Owumi

    2015-01-01

    Specifically, our result indicates unacceptably high levels of aluminum in Eko and Omumu (>10-fold greater than the highest desirable levels set by the USEPA. The aluminum concentrations were influenced by the pH condition in which the samples were digested. Dietary exposure to aluminum at such high levels may be deleterious to maternal health and fetal development. Therefore consumption of Eko and Omumu as an antidote to reduce nausea during pregnancy should be discouraged. Future studies are planned to investigate specific impacts on fetal and maternal health and likely teratogenicity in rodent models.

  7. Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery

    Directory of Open Access Journals (Sweden)

    Indu Sen

    2007-01-01

    Full Text Available In a prospective, double blind, randomized trial, 120 children, aged 3-8 years,ASAI-II, undergoing strabismus repair were randomly divided into three groups (n = 40 each. Oral clonidine premedication (4gg.kg-1 was administered to all the patients two hours prior to surgery. Soon after induction of anaesthesia, Group G patients were administered intravenous granisetron (40gg.kg-1 , Group D intravenous dexamethasone (150gg.kg-1 and group S received 4ml normal saline. Postoperatively, children were continuously monitored and assessed half-hourly till discharge and then after 24 hours for vomiting and pain. The overall incidence of postoperative emesis was lower (15.4% in the Group G compared with the Group D (21.6% in the first 24 hours (P>0.05. The Group S had a highest incidence of postoperative vomiting ((37% P value < 0.0324 compared to group G. The frequency of early vomiting was highest in the S group. Both G and D groups showed better control of delayed emetic episodes. We observed that in children who were premedicated with clonidine, both IV granisetron or dexamethasone were efficacious in reducing the incidence and severity of POV in day-care strabismus surgery.

  8. Anti-emetic activity of Grewia lasiodiscus root extract and fractions

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-03

    Sep 3, 2008 ... peptic ulcer, drug toxicity, myocardial infarction, renal failure, and ... Anhydrous copper sulphate and metoclopramide were obtained from Sigma ... saline/kg. Groups 2, 3, and 4 ... Extract produced significant (P<0.05) dose dependent shortening ... GABA, have been implicated in sleep mechanisms. (Osuide ...

  9. Aprepitant: a promising antiemetic for prevention of chemotherapy-induced nausea and vomiting

    International Nuclear Information System (INIS)

    Aseeri, Mohamad A.

    2006-01-01

    Most patients who undergo chemotherapy have noted that nausea and vomiting are the most feared and distressing side-effects of cancer treatment (1). Nausea and vomiting from chemotherapy can be classified as acute, delayed, or anticipatory. Acute emesis generally occurs within 24 hours of chemotherapy administration; while delayed nausea and vomiting begin 24 hours after chemotherapy and may continue for up to one week. Anticipatory emesis occurs prior to chemotherapy in patients who anticipate another episode by sight, odors or memory of the place where acute nausea and vomiting occurred (2, 3). Different neurotransmitters found in the gastrointestinal tract (GIT) and central nervous system (CNS) mediate the pathophysiology of chemotherapy induced nausea and vomiting (CINV). These include dopamine, histamine, acetycholine, serotonin, and substance P; which act directly and indirectly on the vomiting center located in the lateral reticular formation of the medulla (1, 4). Substance P is a member of the tachykinins family of neuropeptides. The biological activity of this substance is to induce vomiting mediated by neurokinin-1 (NK1) receptors located primarily in the GIT and the CNS (5). Both Nk1 receptors and substance P play a significant role in the pathogenesis of acute and delayed CINV. (author)

  10. Tetrahydrocannabinol vs. Prochlorperazine: the effects of two antiemetics on patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    Ungerleider, J.T.; Andrysiak, T.A.; Fiarbanks, L.A.; Tesler, A.S.; Parker, R.G.

    1984-01-01

    The authors tested the effectiveness of orally administred delta-9-tetrahydrocannabinol (THC) as compared to prochlorperazine for the alleviation of symptoms, such as vomiting and nausea, experienced by patients receiving radiotherapy. The test subjects rated the severity of their illness, as well as the extent of their subsequent moods, their level of concentration, their amount of physical activity, and their desire for social interaction. They chose the drug they preferred and recorded its side effects. The use of THC was slightly more beneficial than the use of prochlorperazine

  11. Domperidone prolongs oral to duodenal transit time in video capsule endoscopy.

    Science.gov (United States)

    Mcfarlane, Michael; Liu, B; Nwokolo, C

    2018-04-01

    Domperidone is thought to accelerate gastric emptying via D2 receptor antagonism at the gastro-oesophageal and gastro-duodenal junctions. Listed in the BNF as a prokinetic anti-emetic, it has been used in video capsule endoscopy (VCE) to accelerate capsule delivery to the small intestine. We audited VCEs performed at UHCW from 2011, when as standard practice, domperidone was given pre-VCE, to 2012, after its discontinuation due to doubts about its effectiveness. Thirty-one patients received oral domperidone 20 mg pre-VCE. Thirty-three patients underwent VCE without domperidone pre-treatment. After 2 h, if the capsule remained intra-gastric, gastroscopy-assisted duodenal delivery was performed. Data was analysed using Mann-Whitney testing. Median oro-duodenal transit was 13 and 30 min in the untreated and domperidone groups, respectively (p = 0.01). Median oro-caecal transit was 242 and 267 min in the untreated and domperidone groups, respectively (p = 0.02). No difference in duodenal-caecal transit was seen (p = 0.60). Six percent of untreated and 13% of domperidone VCEs required gastroscopy-assisted duodenal capsule delivery (p = 0.65). Unexpectedly domperidone delayed VCE gastric transit. Most studies on domperidone prokinetic effects have been in diabetic gastroparesis, demonstrating that domperidone can achieve good symptomatic relief, but with mixed results for gastric emptying. Our study suggests that any antiemetic effects of domperidone are not mediated through accelerated gastric transit.

  12. Formulation and evaluation of bilayer tablets of metoclopramide hydrochloride and diclofenac sodium.

    Science.gov (United States)

    Gattani, Surendra G; Khabiya, Sohan S; Amrutkar, Jitendra R; Kushare, Sachin S

    2012-01-01

    The main objective of the present research work was to develop a bilayer tablet of metoclopramide hydrochloride (MTH) and diclofenac sodium (DS) in separate layers to avoid incompatibility and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine headaches. MTH and DS were formulated as immediate and sustained release layers respectively. In vitro dissolution kinetic studies of an optimized (D10) batch of DS in both sustained release layer and bilayer tablet forms show good linearity of regression coefficient 0.9773 (first order equation). The results reveal that an optimized immediate release layer (M5) of MTH and a sustained release layer (D10) of DS might be suitable for the treatment of migraine by sequential release of the two drugs in a bilayer tablet. Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.

  13. Dgroup: DG01671 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 3 ... Trimethobenzamide hydrochloride (USP) ... Gastrointestinal agent ... DG01762 ... Antiemetic ... DG01783 ... Benzamide type antiemetic ... Antiemetics, benzamides DRD2 [HSA:1813] [KO:K04145] ...

  14. Estudo comparativo de antieméticos e suas associações, na prevenção de náuseas e vômitos pós-operatórios, em pacientes submetidas a procedimentos cirúrgicos ginecológicos Estudio comparativo de antieméticos y sus asociaciones, en la prevención de náusea y vómito postoperatorios, en pacientes sometidas a procedimientos quirúrgicos ginecológicos Comparative study of anti-emetics and their association, in the prevention of postoperative nausea and vomiting in patients undergoing gynecologic surgeries

    Directory of Open Access Journals (Sweden)

    Taylor Brandão Schnaider

    2008-12-01

    . MÉTODO: Setenta pacientes, ASA I y II, fueron sometidas a procedimientos quirúrgicos ginecológicos, bajo bloqueo epidural asociado a la anestesia general. En el Grupo Metoclopramida (GM, se administró 20 mg; en el Grupo Dexametasona (GDe, se inyectó 8 mg; en el Grupo Droperidol (GDr se administró 1,25 mg; en el Grupo Ondansetron (GO se inyectó 8mg; en el Grupo Dexametasona-Ondansetron (GDeO se administró respectivamente 8 mg y 4mg; en el Grupo Droperidol-Ondansetron (GDrO se inyectó 1,25 mg y 4 mg; en el Grupo Dexametasona-Droperidol-Ondansetron (GDeDrO se administró 8mg, 0,625 mg y 4mg. La presencia de náuseas y vómitos fue observada en los momentos de 6, 12, 24 y 36 horas después del término de la operación. RESULTADOS: La incidencia total de episodios de náuseas fue de 4 en el GDeDrO, 6 en el GO, 6 en el GDrO, 11 en el GDe, 11 en el GDeO, 18 en el GM y 22 en el GDr. Al aplicar el test del Chi-cuadrado o el test de Fisher, se comprobó la diferencia estadística significativa entre el GDr y los grupos GDe, GDO, GDrO, GDeO, GDeDrO; entre el GM y los grupos GO, GDrO y GDeDrO; entre el GDeO y el grupo GDeDrO. La incidencia total de episodios de vómitos fue de 3 en el GO, 3 en el GDeDrO, 6 en el GDrO, 7 en el GDe, 7 en el GDeO, 10 en el GDr y 13 en el G. Se comprobó así mismo, la diferencia estadística significativa entre el GDr y los grupos GO y GDeDrO; entre el GM y los grupos GO y GDeDrO. CONCLUSIONES: La asociación dexametasona-droperidol-ondansetron y el ondansetron fueron más eficaces en la profilaxis de náuseas y vómitos.BACKGROUND AND OBJECTIVES: Prophylaxis of postoperative nausea and vomiting has been the subject of several studies. The objective of the present study was to compare anti-emetics, and their association, in the prevention of postoperative nausea and vomiting. METHODS: Seventy patients, ASA I and II, underwent epidural block associated with general anesthesia for gynecologic surgeries. Patients in the Metochlopramide Group

  15. Cathodic adsorptive stripping voltammetry of an anti-emetic agent Granisetron in pharmaceutical formulation and biological matrix

    Directory of Open Access Journals (Sweden)

    Rajeev Jain

    2012-12-01

    Full Text Available Granisetron showed one well-defined reduction peak at Hanging Mercury Drop Electrode (HMDE in the potential range from −1.3 to −1.5 V due to reduction of C=N bond. Solid-phase extraction technique was employed for extraction of Granisetron from spiked human plasma. Granisetron showed peak current enhancement of 4.45% at square-wave voltammetry and 5.33% at cyclic voltammetry as compared with the non stripping techniques. The proposed voltammetric method allowed quantification of Granisetron in pharmaceutical formulation over the target concentration range of 50–200 ng/mL with detection limit 13.63 ng/mL, whereas in human plasma 50–225 ng/mL with detection limit 11.75 ng/mL. Keywords: Granisetron, Human plasma, Solid-phase extraction, Pharmaceutical formulation, Voltammetry, Hanging mercury drop electrode

  16. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  17. Anxiolytic and free radical scavenging potential of Chinese celery (Apium graveolens extract in mice

    Directory of Open Access Journals (Sweden)

    Supita Tanasawet

    2017-01-01

    Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAO-A activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.

  18. Metabotropic glutamate receptors as a target for anticonvulsant and anxiolytic action in immature rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Mikulecká, Anna; Tichá, Kateřina; Lojková-Janečková, Denisa; Kubová, Hana

    2010-01-01

    Roč. 51, Suppl.3 (2010), s. 24-26 ISSN 0013-9580 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabotropic glutamate receptors * pharmacology * development Subject RIV: FH - Neurology Impact factor: 3.955, year: 2010

  19. The Anxiolytic Effect of Aromatherapy on Patients Awaiting Ambulatory Surgery: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Cheng-Hua Ni

    2013-01-01

    Full Text Available The aim of this study was to determine if aromatherapy could reduce preoperative anxiety in ambulatory surgery patients. A total of 109 preoperative patients were randomly assigned to experimental (bergamot essential oil and control (water vapor conditions and their responses to the State Trait Anxiety Inventory and vital signs were monitored. Patients were stratified by previous surgical experience, but that did not influence the results. All those exposed to bergamot essential oil aromatherapy showed a greater reduction in preoperative anxiety than those in the control groups. Aromatherapy may be a useful part of a holistic approach to reducing preoperative anxiety before ambulatory surgery.

  20. Examining the short-term anxiolytic and antidepressant effect of Floatation-REST

    Science.gov (United States)

    Khalsa, Sahib S.; Yeh, Hung-wen; Wohlrab, Colleen; Simmons, W. Kyle; Stein, Murray B.; Paulus, Martin P.

    2018-01-01

    Floatation-REST (Reduced Environmental Stimulation Therapy) reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety), most (n = 46) with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen’s d > 2). Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p < .0001 for all variables). In reference to a group of 30 non-anxious participants, the effects were found to be more robust in the anxious sample and approaching non-anxious levels during the post-float period. Further analysis revealed that the most severely anxious participants reported the largest effects. Overall, the procedure was well-tolerated, with no major safety concerns stemming from this single session. The findings from this initial study need to be replicated in larger controlled trials, but suggest that Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression. Trial registration: ClinicalTrials.gov NCT03051074 PMID:29394251

  1. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    Science.gov (United States)

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats.

    Science.gov (United States)

    Hughes, Robert N; Otto, Maria T

    2013-01-10

    In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

    OpenAIRE

    Saruta, Juri; To, Masahiro; Sugimoto, Masahiro; Yamamoto, Yuko; Shimizu, Tomoko; Nakagawa, Yusuke; Inoue, Hiroko; Saito, Ichiro; Tsukinoki, Keiichi

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemaggl...

  4. An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

    Science.gov (United States)

    Bottaï, T; Cartault, F; Pouget, R; Blayac, J P; Petit, P

    1995-02-01

    We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

  5. Effect of buspirone: An anxiolytic drug on blood glucose in humans

    OpenAIRE

    Ojha, S. K.; Nandave, M.; Sharma, C.

    2006-01-01

    The present study investigated the effect of an antianxiety drug, buspirone on blood glucose and plasma insulin level concerning the role of 5-HT1A receptors in blood glucose regulation in healthy humans. Twelve healthy male volunteers were administered single oral doses of buspirone (10 mg) or placebo, in a randomized, crossover way, followed by oral glucose load (75 gm in 200 ml) at reported Tmax i.e. the time of peak plasma concentration of the respective administered drug. The blood sampl...

  6. Differences in the duration of sedative and anxiolytic effects of desmethyldiazepam in two outbred Wistar strains

    NARCIS (Netherlands)

    van der Laan, J W; de Boer, S.F.; van der Gugten, J; de Groot, G

    Different sensitivities to benzodiazepines have been described for various strains of both rats and mice suggesting that variations in biological features of the animals are responsible for these differences. Since all reports concern inbred strains, we studied two outbred Wistar strains which are

  7. Anxiolytic-Like Effects of Increased Ghrelin Receptor Signaling in the Amygdala

    DEFF Research Database (Denmark)

    Jensen, Morten; Ratner, Cecilia; Rudenko, Olga

    2016-01-01

    BACKGROUND: Besides the well-known effects of ghrelin on adiposity and food intake regulation, the ghrelin system has been shown to regulate aspects of behavior including anxiety and stress. However, the effect of virus-mediated overexpression of the ghrelin receptor in the amygdala has...... not previously been addressed directly. METHOD: First, we examined the acute effect of peripheral ghrelin administration on anxiety- and depression-like behavior using the open field, elevated plus maze, forced swim and tail suspension tests. Next, we examined the effect of peripheral ghrelin administration...... and ghrelin receptor deficiency on stress in a familiar and social environment using the Intellicage system. Importantly, we also used a novel approach to study ghrelin receptor signaling in the brain by overexpressing the ghrelin receptor in the amygdala. We examined the effect of ghrelin receptor...

  8. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats

    NARCIS (Netherlands)

    Godlevsky, L.S.; Muratova, T.N.; Kresyun, N.V.; Luijtelaar, E.L.J.M. van; Coenen, A.M.L.

    2014-01-01

    Anxiety and depression are component of interictal behavioral deteriorations that occur as a consequence of kindling, a procedure to induce chronic epilepsy. The aim of this study was to evaluate the possible effects of electrical stimulation (ES) of paleocerebellar cortex on anxiety and

  9. Sedative and anxiolytic effects of the extracts of the leaves of ...

    African Journals Online (AJOL)

    The leaves are used ethnomedicinally in Nigeria and other parts of the world for insomnia and anxiety among other uses. The investigations sought scientific evidence for the ethnomedicinal use of the leaves for the management of insomnia and anxiety as well as the neural mechanisms for the activities. The sedative and ...

  10. Examining the short-term anxiolytic and antidepressant effect of Floatation-REST.

    Science.gov (United States)

    Feinstein, Justin S; Khalsa, Sahib S; Yeh, Hung-Wen; Wohlrab, Colleen; Simmons, W Kyle; Stein, Murray B; Paulus, Martin P

    2018-01-01

    Floatation-REST (Reduced Environmental Stimulation Therapy) reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety), most (n = 46) with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen's d > 2). Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression. ClinicalTrials.gov NCT03051074.

  11. Examining the short-term anxiolytic and antidepressant effect of Floatation-REST.

    Directory of Open Access Journals (Sweden)

    Justin S Feinstein

    Full Text Available Floatation-REST (Reduced Environmental Stimulation Therapy reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety, most (n = 46 with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen's d > 2. Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p < .0001 for all variables. In reference to a group of 30 non-anxious participants, the effects were found to be more robust in the anxious sample and approaching non-anxious levels during the post-float period. Further analysis revealed that the most severely anxious participants reported the largest effects. Overall, the procedure was well-tolerated, with no major safety concerns stemming from this single session. The findings from this initial study need to be replicated in larger controlled trials, but suggest that Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression.ClinicalTrials.gov NCT03051074.

  12. Anxiolytic effects of GLYX-13 in animal models of posttraumatic stress disorder-like behavior.

    Science.gov (United States)

    Jin, Zeng-Liang; Liu, Jin-Xu; Liu, Xu; Zhang, Li-Ming; Ran, Yu-Hua; Zheng, Yuan-Yuan; Tang, Yu; Li, Yun-Feng; Xiong, Jie

    2016-09-01

    In the present study, we investigated the effectiveness of GLYX-13, an NMDA receptor glycine site functional partial agonist, to alleviate the enhanced anxiety and fear response in both a mouse and rat model of stress-induced behavioral changes that might be relevant to posttraumatic stress disorder (PTSD). Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent findings in stress-related disease. Herein, we used these animal models to further investigate the effect of GLYX-13 on the stress hormone levels and glucocorticoid receptor (GR) expression. We found that exposure to foot shock induced long-lasting behavioral deficiencies in mice, including freezing and anxiety-like behaviors, that were significantly ameliorated by the long-term administration of GLYX-13 (5 or 10 mg/kg). Our enzyme-linked immunosorbent assay results showed that long-term administration of GLYX-13 at behaviorally effective doses (5 or 10 mg/kg) significantly decreased the elevated serum levels of both corticosterone and its upstream stress hormone adrenocorticotropic hormone in rats subjected to the TDS procedure. These results suggest that GLYX-13 exerts a therapeutic effect on PTSD-like stress responding that is accompanied by (or associated with) modulation of the HPA axis, including inhibition of stress hormone levels and upregulation of hippocampal GR expression. © The Author(s) 2016.

  13. Treatment of nausea and vomiting in terminally ill cancer patients.

    Science.gov (United States)

    Glare, Paul A; Dunwoodie, David; Clark, Katherine; Ward, Alicia; Yates, Patsy; Ryan, Sharon; Hardy, Janet R

    2008-01-01

    Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.

  14. Acute Dystonia in a Child Receiving Metoclopramide: Case Report

    Directory of Open Access Journals (Sweden)

    Alaaddin Yorulmaz

    2016-11-01

    Full Text Available Metoclopramide is a benzamide that is a dopamine receptor, often preferred as a prokinetic agent to accelerate gastrointestinal passage in the treatment of gastroesophageal reflux disease; itis also used as an antiemetic agent in many diseases that progress with nausea-vomiting. It is effective on the digestive system both centrally and peripherally. It easily overcomes the blood-brain barrier and may create side effects pertaining to the extrapyramidal system. Acute dystonic reaction is rare among these side effects; it is, however, a condition that needs to be treated urgently. This paper presents a 5-month-old infant patient who developed acute dystonic reaction secondary to the use of Metpamid at a high dose. The diagnosis in this case was made based onpatient history. The patient%u2019s symptoms rapidly disappeared thanks to treatment with diphenhydramine. It should be remembered that metoclopramide may cause side effects in patients presenting to the emergency service with acute dystonia, soa complete history of drugs should definitely be taken for such patients.

  15. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery.

    LENUS (Irish Health Repository)

    Szarvas, Szilvia

    2012-02-03

    In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus. IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.

  16. Double-blind comparative study of droperidol, granisetron and granisetron plus dexamethasone as prophylactic anti-emetic therapy in patients undergoing abdominal, gynaecological, breast or otolaryngological surgery

    NARCIS (Netherlands)

    Janknegt, R; Pinckaers, JWM; Rohof, MHC; Ausems, MEM; Arbouw, MEL; van der Velden, RW; Brouwers, JRBJ

    In this double-blind study the clinical efficacy of a single pre-operative intravenous dose of droperidol 1.25 mg (137 patients), granisetron 1 mg (130 patients) and granisetron 1 mg plus dexamethasone 5 mg (130 patients) was investigated for the prevention of postoperative nausea and vomiting after

  17. The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

    Science.gov (United States)

    Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

    2017-10-01

    Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

  18. Effect of anxiolytic aphobazole on hemopoietic system under exposure to low doses of ionizing radiation and emotional stress

    International Nuclear Information System (INIS)

    Moroz, B.B.; Deshevoj, Yu.B.; Seredenin, S.B.; Lyrshchikova, A.V.; Lebedev, V.G.

    2001-01-01

    Effect of aphobazole in investigated on the course of adaptation reactions and state of compensatory capabilities of hemopoietic system of rats-males under long-term emotional stress developed following the low-dose gamma-radiation. Gamma-quanta from 137 Cs source at 0.9 Gy dose (1.3 Gy/min dose rate) were used for single and uniform irradiation of animals. Two days later rats were exposed to long-term emotional stress. Aphobazole at the dose of 10.0 mg/kg was incorporated into rats once a day. It is shown that aphobazole permits to stop the violations in adaptation reactions and compensatory capabilities of hemopoietic system under conditions of emotional stress development in the early period following the exposure to gamma radiation at 0.9 Gy dose [ru

  19. Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Kellner, M; Porseryd, T; Hallgren, S; Porsch-Hällström, I; Hansen, S H; Olsén, K H

    2016-04-01

    Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents and surface waters around the world. Citalopram and other selective serotonin re-uptake inhibitors have, at concentrations that occur in nature, been shown to have behavioural as well as physiological effects on fish and other animals. This study is the result of several different experiments, intended to analyse different aspects of behavioural effects of chronic citalopram exposure in fish. Our model species the three-spine stickleback is common in the entire northern hemisphere and is considered to be a good environmental sentinel species. Female three-spine sticklebacks were exposed to 0, 1.5 and 15μg/l nominal concentrations of citalopram for 21 days and subjected to the novel tank (NT) diving test. In the NT test, the fish exposed to 1.5μg/l, but not the 15μg/l fish made a significantly higher number of transitions to the upper half and stayed there for significantly longer time than the fish exposed to 0μg/l. The 15μg/l group, however, displayed a significantly lower number of freeze bouts and a shorter total freezing time. The test for locomotor activity included in the NT test showed that fish treated with 1.5 and 15μg/l displayed a significantly higher swimming activity than control fish both 5-7 and 15-17min after the start of the experiment. In the next experiment we compared fish exposed to 1.5μg/l and 0.15μg/l to pure water controls with regard to shoaling intensity and found no effect of treatment. In the final experiment the propensity of fish treated with 1.5μg/l to approach an unknown object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically significant effects. It is concluded that citalopram changes the behaviour of the three-spine stickleback in a way that is likely to have ecological consequences and that it must not be considered an environmentally safe pharmaceutical. Copyright © 2016. Published by Elsevier B.V.

  20. Treatment Related Thoughts Based on Health Belief Model and Medication Nonadherence in Patients who Prescribed Anxiolytics and Antidepressants

    Directory of Open Access Journals (Sweden)

    Meltem Meric

    2010-10-01

    Full Text Available AIM: The purpose of this study was to evaluate the relationship between treatment adherence and treatment related thoughts based on health belief model in patients who currently take medication due to depression and anxiety disorder. METHOD: The present study was performed at the Psychiatry Department of a teaching hospital. The sample of the study consisted from 112 individuals who take medications due to depression and anxiety disorder. Personal information form and an inquiry form including treatment related thoughts based on health belief model were used to collect data. Chi- Square and Percentages were used for statistical analysis. RESULTS: Of the patients, 58.9% were diagnosed as depression and 41.1% anxiety disorder. 60.7% stated that they had a non-adherence experience in the past. Of these non-adherent patients, 29.5% stopped to take the medication with the idea “I can do it without medication” and 14.3% stopped the medication because of the side effects. Gender, age, marital status and education level were not related to the non-adherence. Only two treatment related thoughts based on health belief concepts were significantly related to the non adherence experience. These thoughts were “If I do not take the medications properly the problems may be permanent” and “If I do not take the medications properly my illness may get worse”. Most of the patients marked “agree” options of the items under the perceived severity, self-efficacy, benefits, susceptibility and health motivation subheads. CONCLUSION: The results of this study showed that the thoughts and perceptions based on health belief concepts helps to identify and express the thoughts related to treatment adherence. These concepts can be used to describe and classify the thoughts about the treatments of patients. However, prospective and qualitative studies may be useful to clarify the influence of the health beliefs on treatment adherence. [TAF Prev Med Bull 2010; 9(5.000: 441-452

  1. A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice

    Directory of Open Access Journals (Sweden)

    Natasha Maurmann

    2011-01-01

    Full Text Available Plants of the genus Valeriana (Valerianaceae are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries. This study was undertaken to explore the neurobehavioral effects of systemic administration of a valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil in mice. Adult animals were treated with a single intraperitoneal injection of valepotriate fraction (VF in the concentrations of 1, 3 or 10 mg kg-1, or with vehicle in the pre-training period before each behavioral test. During the exploration of an open field, mice treated with 10 mg kg-1 of VF showed reduced locomotion and exploratory behavior. Although overall habituation sessions for locomotion and exploratory behavior among vehicle control and doses of VF were not affected, comparison between open-field and habituation sessions within each treatment showed that VF administration at 1 and 10 mg kg-1 impaired habituation. In the elevated plus-maze test, mice treated with VF (10 mg kg-1 showed a significant increase in the percentage of time spent in the open arms without significant effects in the number of total arm entries. VF at 3 mg kg-1 produced an impairment of novel-object recognition memory. In contrast, VF did not affect fear-related memory assessed in an inhibitory avoidance task. The results indicate that VF can have sedative effects and affect behavioral parameters related to recognition memory.

  2. Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

    Science.gov (United States)

    Kouzani, Abbas Z; Kale, Rajas P; Zarate-Garza, Pablo Patricio; Berk, Michael; Walder, Ken; Tye, Susannah J

    2017-09-01

    Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.

  3. Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Hye Young Ji

    2012-01-01

    Full Text Available DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP enzymes and four UDP-glucuronosyltransferase (UGT enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50 values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol 1′-hydroxylation with an inhibition constant (Ki value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol 1′-hydroxylation, with a Ki value of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50 equivalent concentration (volume per dose index value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate the in vivo extent of the observed in vitro interactions.

  4. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias

    Science.gov (United States)

    Cubeddu, Luigi X.

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended. PMID:26926294

  5. Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

    Science.gov (United States)

    Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

    2016-01-01

    Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. Safety and side effects of cannabidiol, a Cannabis sativa constituent.

    Science.gov (United States)

    Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S

    2011-09-01

    Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

  7. Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus)

    DEFF Research Database (Denmark)

    Kellner, M; Porseryd, T; Hallgren, S

    2016-01-01

    Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents...... object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically...

  8. Aprendizagem de procedimentos e efeitos ansiolíticos: medidas eletrencefalográficas, motora e atencional Procedural learning and anxiolytic effects: electroencephalographic, motor and attentional measures

    Directory of Open Access Journals (Sweden)

    Claudio Elidio Portella

    2006-06-01

    Full Text Available O objetivo do presente estudo foi avaliar parâmetros atencionais, motores e eletrencefalográficos durante uma tarefa de procedimentos em sujeitos que ingeriram 6mg de bromazepam. A amostra consistiu de 26 sujeitos saudáveis, ambos os sexos, entre 19 e 36 anos. Os grupos controle e experimental foram submetidos à tarefa datilográfica em desenho duplo-cego randomizado. Os achados não revelaram diferenças nas medidas atencionais e motoras entre os grupos. Foram avaliadas medidas de coerência (EEGq entre regiões do escalpo nas bandas teta, alfa e beta. Análise inicial revelou um efeito principal para condição (Anova 2- critérios de variação - condição versus blocos. Uma segunda Anova, também com 2 critérios de variação (condição versus região do escalpo, demonstrou um efeito principal para ambos os fatores. Em conclusão, a medida de coerência parece não ser uma ferramenta sensível para demonstrar diferenças entre áreas corticais em função de uma tarefa de procedimentos.The objective of the present study was to evaluate attentional, motor and electroencephalographic (EEG parameters during a procedural task when subjects have ingested 6mg of bromazepam. The sample consisted of 26 healthy subjects, male or female, between 19 and 36 years of age. The control (placebo and experimental (bromazepam 6mg groups were submitted to a typewriting task in a randomized, double-blind design. The findings did not show significant differences in attentional and motor measures between groups. Coherence measures (qEEG were evaluated between scalp regions, in theta, alpha and beta bands. A first analysis revealed a main effect for condition (Anova-2way - condition versus blocks. A second Anova 2-way (condition versus scalp regions showed a main effect for both factors. The coherence measure was not a sensitive tool at demonstrating differences between cortical areas as a function of procedural learning.

  9. Ablation of kappa-opioid receptors from brain dopamine neurons has anxiolytic-like effects and enhances cocaine-induced plasticity.

    Science.gov (United States)

    Van't Veer, Ashlee; Bechtholt, Anita J; Onvani, Sara; Potter, David; Wang, Yujun; Liu-Chen, Lee-Yuan; Schütz, Günther; Chartoff, Elena H; Rudolph, Uwe; Cohen, Bruce M; Carlezon, William A

    2013-07-01

    Brain kappa-opioid receptors (KORs) are implicated in states of motivation and emotion. Activation of KORs negatively regulates mesolimbic dopamine (DA) neurons, and KOR agonists produce depressive-like behavioral effects. To further evaluate how KOR function affects behavior, we developed mutant mice in which exon 3 of the KOR gene (Oprk1) was flanked with Cre-lox recombination (loxP) sites. By breeding these mice with lines that express Cre-recombinase (Cre) in early embryogenesis (EIIa-Cre) or only in DA neurons (dopamine transporter (DAT)-Cre), we developed constitutive KOR knockouts (KOR(-/-)) and conditional knockouts that lack KORs in DA-containing neurons (DAT-KOR(lox/lox)). Autoradiography demonstrated complete ablation of KOR binding in the KOR(-/-) mutants, and reduced binding in the DAT-KOR(lox/lox) mutants. Quantitative reverse transcription PCR (qPCR) studies confirmed that KOR mRNA is undetectable in the constitutive mutants and reduced in the midbrain DA systems of the conditional mutants. Behavioral characterization demonstrated that these mutant lines do not differ from controls in metrics, including hearing, vision, weight, and locomotor activity. Whereas KOR(-/-) mice appeared normal in the open field and light/dark box tests, DAT-KOR(lox/lox) mice showed reduced anxiety-like behavior, an effect that is broadly consistent with previously reported effects of KOR antagonists. Sensitization to the locomotor-stimulating effects of cocaine appeared normal in KOR(-/-) mutants, but was exaggerated in DAT-KOR(lox/lox) mutants. Increased sensitivity to cocaine in the DAT-KOR(lox/lox) mutants is consistent with a role for KORs in negative regulation of DA function, whereas the lack of differences in the KOR(-/-) mutants suggests compensatory adaptations after constitutive receptor ablation. These mouse lines may be useful in future studies of KOR function.

  10. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    Science.gov (United States)

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  11. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    Science.gov (United States)

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  12. S32006, a novel 5-HT(2C) receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models

    NARCIS (Netherlands)

    Dekeyne, Anne; la Cour, Clotilde Mannoury; Gobert, Alain; Brocco, Mauricette; Lejeune, Francoise; Serres, Florence; Sharp, Trevor; Daszuta, Annie; Soumier, Amelie; Papp, Mariusz; Rivet, Jean-Michel; Flik, Gunnar; Cremers, Thomas I.; Muller, Olivier; Lavielle, Gilbert; Millan, Mark J.

    Rationale Serotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states. Objectives Herein, we characterized the in vitro and in vivo pharmacological profile of the novel benzourea derivative, S32006.

  13. Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice.

    Science.gov (United States)

    Hatoum, Hind T; Lin, Swu-Jane; Buchner, Deborah; Cox, David

    2012-05-01

    The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT(3) RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions. PharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT(3) RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days. Of the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT(3) RA regimens.

  14. Systemisk prokinetisk behandling af postoperativ ileus efter abdominalkirurgi. Gennemgang af et Cochrane-review

    DEFF Research Database (Denmark)

    Holte, Kathrine

    2010-01-01

    Based on the evidence presented in the Cochrane review "Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults", routine administration of systemic prokinetics for the prevention of postoperative ileus is not recommendable. The potential...... of selective opioid antagonists and intravenous lidocaine should be further investigated, particularly in conjunction with laparoscopic surgery, epidural pain management and fast-track surgery....

  15. Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review

    Science.gov (United States)

    2013-01-01

    Background Levomepromazine is an antipsychotic drug that is used clinically for a variety of distressing symptoms in palliative and end-of-life care. We undertook a systematic review based on the question “What is the published evidence for the use of levomepromazine in palliative symptom control?”. Methods To determine the level of evidence for the use of levomepromazine in palliative symptom control, and to discover gaps in evidence, relevant studies were identified using a detailed, multi-step search strategy. Emerging data was then scrutinized using appropriate assessment tools, and the strength of evidence systematically graded in accordance with the Oxford Centre for Evidence-Based Medicine’s ‘levels of evidence’ tool. The electronic databases Medline, Embase, Cochrane, PsychInfo and Ovid Nursing, together with hand-searching and cross-referencing provided the full research platform on which the review is based. Results 33 articles including 9 systematic reviews met the inclusion criteria: 15 on palliative sedation, 8 regarding nausea and three on delirium and restlessness, one on pain and six with other foci. The studies varied greatly in both design and sample size. Levels of evidence ranged from level 2b to level 5, with the majority being level 3 (non-randomized, non-consecutive or cohort studies n = 22), with the quality of reporting for the included studies being only low to medium. Conclusion Levomepromazine is widely used in palliative care as antipsychotic, anxiolytic, antiemetic and sedative drug. However, the supporting evidence is limited to open series and case reports. Thus prospective randomized trials are needed to support evidence-based guidelines. PMID:23331515

  16. Cannabidiol in Humans—The Quest for Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Stéphane Potvin

    2012-05-01

    Full Text Available Cannabidiol (CBD, a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies, schizophrenia and bipolar mania (four studies, social anxiety disorder (two studies, neuropathic and cancer pain (two studies, cancer anorexia (one study, Huntington’s disease (one study, insomnia (one study, and epilepsy (one study. Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.

  17. From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

    Science.gov (United States)

    Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza

    2015-12-01

    5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

  18. [Phytobezoar dissolution with Coca-Cola].

    Science.gov (United States)

    Martínez de Juan, F; Martínez-Lapiedra, C; Picazo, V

    2006-05-01

    The treatment of phytobezoar is empiric. The various therapeutic choices include dietary modifications, prokinetic drugs, gastric lavage, enzymatic dissolution, endoscopic treatment, and surgery. We present two cases of phytobezoar with successful outcome after Coca-Cola administration.

  19. Correlation of bowel symptoms with colonic transit, length, and faecal load in functional faecal retention

    DEFF Research Database (Denmark)

    Raahave, Dennis; Christensen, Elsebeth; Loud, Franck B.

    2009-01-01

    INTRODUCTION: Abdominal pain, bloating, and defecation disturbances are common complaints in gastrointestinal functional disorders. This study explores whether bowel symptoms are correlated to colon transit time (CTT), faecal loading (coprostasis), and colon length; and whether prokinetic interve...

  20. The relation between gastro-oesophageal reflux, sleeping-position and sudden infant death and its impact on positional therapy

    NARCIS (Netherlands)

    Vandenplas, Y.; Belli, D. C.; Dupont, C.; Kneepkens, C. M.; Heymans, H. S.

    1997-01-01

    Many infants do regurgitate. The recommended therapeutic approach starts with postural and dietary measures, followed by antacids and prokinetics. However, the recent findings regarding the increased risk for sudden infant death (SID) in the prone sleeping position challenge the current

  1. Treatment of GI dysmotility in scleroderma with the new enterokinetic agent prucalopride

    NARCIS (Netherlands)

    Boeckxstaens, G. E.; Bartelsman, J. F. W. M.; Lauwers, L.; Tytgat, G. N. J.

    2002-01-01

    Scleroderma is a multisystem disorder frequently resulting in disturbed GI motility. Although, especially early in the disease, symptomatic improvement is achieved with prokinetic agents, more severe GI manifestations of scleroderma may be difficult to treat, leading to parenteral feeding and

  2. The effect of a single rectal dose of cisapride on delayed gastric emptying.The effect of a single rectal dose of cisapride on delayed gastric emptying.

    NARCIS (Netherlands)

    Brummer, R.J.M.; Schoenmakers, E.A.J.M.; Kemerink, G.J.; Heidendal, G.A.K.; Sanders, D.G.M.; Stockbrügger, R.W.

    1997-01-01

    Department of Gastroenterology, University Hospital Maastricht, The Netherlands. BACKGROUND: Cisapride has an established prokinetic effect in patients with delayed gastric emptying. However, rectal administration of the drug might be preferred in patients with either dysphagia or nausea due to

  3. Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs) : A methodological approach to assess consistencies across databases from the PROTECT-EU project

    NARCIS (Netherlands)

    Requena, Gema; Huerta, Consuelo; Gardarsdottir, Helga; Logie, John; González-González, Rocío; Abbing-Karahagopian, Victoria; Miret, Montserrat; Schneider, Cornelia; Souverein, Patrick C.; Webb, Dave; Afonso, Ana; Boudiaf, Nada; Martin, Elisa; Oliva, Belén; Alvarez, Arturo; de Groot, Mark C H; Bate, Andrew; Johansson, Saga; Schlienger, Raymond; Reynolds, Robert; Klungel, Olaf H.; de Abajo, Francisco J.

    2016-01-01

    Background: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. Objectives: The objectives of this paper were to evaluate the impact of applying a

  4. Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs) : a methodological approach to assess consistencies across databases from the PROTECT-EU project

    NARCIS (Netherlands)

    Requena, Gema; Huerta, Consuelo; Gardarsdottir, Helga; Logie, John; González-González, Rocío; Abbing-Karahagopian, Victoria; Miret, Montserrat; Schneider, Cornelia; Souverein, Patrick C; Webb, Dave; Afonso, Ana; Boudiaf, Nada; Martin, Elisa; Oliva, Belén; Alvarez, Arturo; De Groot, Mark C H; Bate, Andrew; Johansson, Saga; Schlienger, Raymond; Reynolds, Robert; Klungel, Olaf H; de Abajo, Francisco J

    2016-01-01

    BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a

  5. 2016 Updated MASCC/ESMO Consensus Recommendations

    DEFF Research Database (Denmark)

    Olver, Ian; Ruhlmann, Christina H.; Jahn, Franziska

    2017-01-01

    the MASCC antiemetic guidelines. A subgroup performed a systematic literature review on antiemetics for low emetogenic chemotherapy (LEC) and chemotherapy of minimal emetic potential and the chair presented the update recommendation to the whole group for discussion. They then voted with an aim of achieving...

  6. Osteonecrosis in patients with testicular tumours treated with chemotherapy.

    NARCIS (Netherlands)

    Berkmortel, F.W.P.J. van den; Wit, R. de; Rooy, J.W.J. de; Mulder, P.H.M. de

    2004-01-01

    The role of antiemetics is invaluable in allowing cancer patients to complete, otherwise possibly intolerable, chemotherapy. In the Perugia Consensus Conference it was decided that the recommended antiemetic regimen in the prevention of acute emesis induced by a single high, low and repeated doses

  7. Fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H. B.; Herrstedt, Jørn

    2012-01-01

    For patients receiving cancer chemotherapy, the ongoing development of antiemetic treatment is of significant importance. Patients consider nausea and vomiting among the most distressing symptoms of chemotherapy, and as new antiemetics have been very successful in prevention of vomiting, agents...... intravenous dose of 150 mg can replace the aprepitant 3-day oral regimen. This article focuses on the development and clinical application of fosaprepitant....

  8. 2016 updated MASCC/ESMO consensus recommendations

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H.; Jahn, Franziska; Jordan, Karin

    2017-01-01

    Purpose: Radiotherapy-induced nausea and vomiting (RINV) are distressing symptoms. Evidence-based guidelines should facilitate the prescription of the best possible antiemetic prophylaxis. As part of the MASCC/ESMO Antiemetic Guidelines Update 2016, a thorough review of the literature concerning ...

  9. Palonosetron and prednisolone for the prevention of nausea and emesis during fractionated radiotherapy and 5 cycles of concomitant weekly cisplatin-a phase II study

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H; Belli, Charlotte; Dahl, Tina

    2013-01-01

    Recommendations for antiemetic prophylaxis supportive to radiotherapy and concomitant chemotherapy are not evidence-based. The purpose of this study was to evaluate the efficacy of the antiemetic regimen concurrent to fractionated radiotherapy and concomitant weekly cisplatin in two Danish depart...

  10. Reducing radiation induced emesis in abdominal radiotherapy

    International Nuclear Information System (INIS)

    Griffin, K.

    1994-01-01

    In patients with seminoma testes, a comparison was made between radiation induced emesis suffered by patients receiving 'dogleg' radiotherapy with those suffered by patients who received para-aortic radiotherapy. The same comparisons were made between the effects suffered by those patients who received the anti-emetic, Ondansetron, and those suffered by patients who received conventional anti-emetics. (UK)

  11. New treatments on the horizon for chemoradiotherapy-induced nausea and vomiting

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H; Herrstedt, Jørn

    2016-01-01

    the proper timing, duration, and combination of antiemetic drugs for the prevention of chemoradiotherapy-induced nausea and vomiting (C-RINV). AREAS COVERED: The article summarises the available antiemetic studies, the evidence for antiemetic prophylaxis of C-RINV, and the future perspectives for antiemetic...... research in chemoradiotherapy. EXPERT OPINION: Antiemetic prophylaxis for patients receiving concomitant chemoradiotherapy has, for many years, been an orphan research area. The distinction between acute and delayed nausea and vomiting does not apply to fractionated radiotherapy, and prophylaxis should...... be considered to cover the entire course of treatment and not only the acute and delayed chemotherapy-induced nausea and vomiting. The best prophylaxis in women receiving fractionated radiotherapy and concomitant weekly cisplatin is a combination of the neurokinin receptor antagonist fosaprepitant...

  12. Interaction Between the Cannabinoid and Vanilloid Systems on Anxiety in Male Rats

    Directory of Open Access Journals (Sweden)

    Nafiseh Faraji

    2017-03-01

    Conclusion: Acute neuropharmacological blockade of the TRPV1 receptor or stimulation of the CB1 receptor produced an anxiolytic effect. It seems that antagonism of the vanilloid system modulates cannabinoid outputs that increase the anxiolytic effect. TRPV1 antagonism may alter endocannabinoids production, which in turn enhances anxiolytic effect. These results suggest interaction of two systems or sharing some signaling pathways that affect anxiety expression.

  13. Effect of postoperative experiences on willingness to pay to avoid postoperative pain, nausea, and vomiting

    NARCIS (Netherlands)

    van den Bosch, Jolanda E.; Bonsel, Gouke J.; Moons, Karel G.; Kalkman, Cor J.

    2006-01-01

    BACKGROUND: The authors assessed the willingness to pay (WTP) for "perfect" prophylactic antiemetics and analgesics in patients who were scheduled to undergo surgery during general anesthesia. Furthermore, they determined whether postoperative experiences of pain and nausea and vomiting (PONV)

  14. A Controlled Study Using Acupuncture as an Adjuvant to Treat Chemotherapy-Induced Nausea and Vomiting

    National Research Council Canada - National Science Library

    Lao, Lixing

    2001-01-01

    ...) on nausea and vomiting induced by chemotherapy in cancer patients. The primary aim of this study is to evaluate the usefulness of EA as an adjuvant on N/V in chemotherapy patients who do not respond to conventional antiemetics...

  15. Rolapitant Injection

    Science.gov (United States)

    ... class of medications called antiemetics. It works by blocking the action of neurokinin and substance P, natural ... swallowing; shortness of breath; swelling of the eyes, face, mouth, tongue, or throat; chest pain; stomach pain ...

  16. Drug: D06574 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ntestinal agent ... DG01762 ... Antiemetic ATC code: A04AD13 Chemical group: DG02244 ... Treatment of unipolar depression, anxiety, and insom...nia disorders, Prevention and treatment of nausea and vomiting, Treatment of functi

  17. Possibilities and shortcomings of maintenance therapy in gastroesophageal reflux disease

    NARCIS (Netherlands)

    Tytgat, G. N.

    1999-01-01

    An overview is given of the current possibilities and shortcomings of medical therapy in reflux disease. With H2-receptor antagonists and prokinetics, roughly 60% of the patients can be maintained in remission; with proton pump inhibitors, remission can be maintained in approximately 90%. Whether

  18. SAJS NEW.indd

    African Journals Online (AJOL)

    (usually 3 times a day) deflation and antegrade enemas (once or twice a day). The patients were discharged as soon as they were capable of using the button colostomy. Prokinetic agents and laxatives were continued as baseline medical treatment after discharge. All patients were followed up regularly. Assessment.

  19. Gongronema Latifolium delays gastric emptying of semi-solid meals ...

    African Journals Online (AJOL)

    The aim of the study was to investigate sonographically the effect of Gongronema latifolium on gastric emptying of semi-solid meals in diabetic dogs. Twenty-five alloxan-induced diabetic dogs were randomly allotted into five groups of five dogs each in a randomised placebo-controlled study. These are placebo, prokinetic ...

  20. Progressive supranuclear palsy syndrome induced by clebopride.

    Science.gov (United States)

    Campdelacreu, Jaume; Kumru, Hatice; Tolosa, Eduard; Valls-Solé, Josep; Benabarre, Antoni

    2004-04-01

    We report on a patient who presented with a progressive supranuclear palsy (PSP) syndrome while receiving clebopride (CLB), a prokinetic drug with central antidopaminergic properties. The clinical and neurophysiological signs progressively disappeared after CLB withdrawal. To our knowledge, this is the first published PSP-like syndrome attributable to an antidopaminergic drug. Copyright 2003 Movement Disorder Society

  1. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects

    NARCIS (Netherlands)

    Kessing, B. F.; Smout, A. J. P. M.; Bennink, R. J.; Kraaijpoel, N.; Oors, J. M.; Bredenoord, A. J.

    2014-01-01

    The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and

  2. Effects of chlordiazepoxide and buspirone on plasma catecholamine and corticosterone levels in rats under basal and stress conditions

    NARCIS (Netherlands)

    de Boer, S.F.; Slangen, J L; van der Gugten, J

    The effects of the classical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-induced plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) release were investigated. Male Wistar rats provided with a

  3. Pattern of prophylaxis administration for chemotherapy-induced nausea and vomiting: an analysis of city-based health insurance data.

    Science.gov (United States)

    Nakamura, Fumiaki; Higashi, Takahiro

    2013-12-01

    Chemotherapy-induced nausea and vomiting (CINV) substantially affects patient quality of life. Although several guidelines have recommended the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists with glucocorticoids to alleviate acute CINV, studies in other countries have reported that these recommendations were often not followed. We aimed to assess antiemetic use in community practices just before the Japanese Guidelines for the Appropriate Use of Antiemetics were published. Using the insurance claims submitted to a public insurance program that covers residents up to 75 years old operated by a city with a population of 250,000, we examined the concurrent use of 5HT3 receptor antagonists and glucocorticoids with high or moderate emetic risk chemotherapy. Overall, 448 patients received high or moderate emetic risk chemotherapy 1,342 times during the study period. The recommended antiemetic therapy was provided in 61.9 % (95 % confidence interval 55.5-68.3 %) of the treated patients, but the moderate emetic risk chemotherapy group received the recommended antiemetic therapy less frequently than the high emetic risk chemotherapy group (55.5 vs. 82.1 %, P chemotherapy were associated with the recommended antiemetic therapy. Breast and lung cancer patients receiving high emetic risk chemotherapy received the recommended antiemetics in 100 % of cases, while only 67 % of patients with other cancer types received the recommended antiemetics. Despite several limitations associated with analysis of insurance claims, our study indicates that substantial room for improvement exists in the practice of preventing CINV.

  4. Control of Nausea and Vomiting in Patients Receiving Anthracycline/Cyclophosphamide Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Nawa-Nishigaki, Minako; Kobayashi, Ryo; Suzuki, Akio; Hirose, Chiemi; Matsuoka, Rie; Mori, Ryutaro; Futamura, Manabu; Sugiyama, Tadashi; Yoshida, Kazuhiro; Itoh, Yoshinori

    2018-02-01

    Chemotherapy-induced nausea and vomiting (CINV) is one of most distressing adverse events during cancer chemotherapy. In breast cancer patients receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly controlled. The prevalence of guideline-consistent antiemetic medication and control of CINV were investigated retrospectively in breast cancer patients receiving the first cycle of AC chemotherapy. Risks for CINV were analyzed by the multivariate logistic regression analysis. The effect of olanzapine added to the standard antiemetic medication on the incidence of CINV was subsequently evaluated in separate patients who received the first cycle of AC chemotherapy. Although the guideline-consistent antiemetic medication was performed in all subjects, the control rate of nausea (32%), but not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year-old was a significant factor that reduces the control of both nausea and vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug antiemetic medication, significantly improved the control of nausea and complete response. CINV was poorly controlled in breast cancer patients receiving AC chemotherapy, in which age younger than 55-year-old was a significant risk for both nausea and vomiting. Olanzapine was effective for improvement of the control of CINV associated with AC chemotherapy. Therefore, care should be taken to prevent CINV in young patients receiving AC chemotherapy by adding olanzapine to the standard three-drug antiemetic medication. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

    Science.gov (United States)

    Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

    2014-12-01

    Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

  6. Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Summers, Yvonne; Daugaard, Gedske

    2018-01-01

    PURPOSE: The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy. METHODS: This dose-finding, non-comparative study investigated the antiemetic effect and safety...... of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0-24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron. The primary parameter was complete response (0...... interval: 65-94%) had a CR and 14/23 (61%) had no nausea at all. CONCLUSIONS: Amisulpride has antiemetic effect against cisplatin-induced acute nausea and vomiting. The effect against nausea is of particular interest. Randomised studies are warranted to further explore the effect and safety of amisulpride....

  7. Impact and management of chemotherapy/radiotherapy-induced nausea and vomiting and the perceptual gap between oncologists/oncology nurses and patients: a cross-sectional multinational survey.

    Science.gov (United States)

    Vidall, Cheryl; Fernández-Ortega, Paz; Cortinovis, Diego; Jahn, Patrick; Amlani, Bharat; Scotté, Florian

    2015-11-01

    Chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV) can affect half of oncology patients, significantly impacting daily life. Nausea without vomiting has only recently been thought of as a condition in its own right. As such, the incidence of nausea is often underestimated. This survey investigated the incidence and impact of CINV/RINV in patients compared with estimations of physicians/oncology nurses to determine if there is a perceptual gap between healthcare professionals and patients. An online research survey of physicians, oncology nurses and patients was conducted across five European countries. Participants had to have experience prescribing/recommending or have received anti-emetic medication for CINV/RINV treatment. Questionnaires assessed the incidence and impact of CINV/RINV, anti-emetic usage and compliance, and attribute importance of anti-emetic medication. A total of 947 (375 physicians, 186 oncology nurses and 386 patients) participated in this survey. The incidence of nausea was greater than vomiting: 60 % of patients reported nausea alone, whereas 18 % reported vomiting. Physicians and oncology nurses overestimated the incidence of CINV/RINV but underestimated its impact on patients' daily lives. Only 38 % of patients reported full compliance with physicians'/oncology nurses' guidelines when self-administering anti-emetic medication. Leading factors for poor compliance included reluctance to add to a pill burden and fear that swallowing itself would induce nausea/vomiting. There is a perceptual gap between healthcare professionals and patients in terms of the incidence and impact of CINV/RINV. This may lead to sub-optimal prescription of anti-emetics and therefore management of CINV/RINV. Minimising the pill burden and eliminating the requirement to swallow medication could improve poor patient compliance with anti-emetic regimens.

  8. Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors

    OpenAIRE

    Endo, Mari; Hori, Masatoshi; Ozaki, Hiroshi; Oikawa, Tetsuro; Hanawa, Toshihiko

    2013-01-01

    Background Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of act...

  9. Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

    OpenAIRE

    Lim, Hyun Chul; Kim, Young Gyun; Lim, Jung Hyun; Kim, Hee Sun; Park, Hyojin

    2008-01-01

    Purpose Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D2 receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. Materials and Methods The distal ileum was excised and the activity of peristaltic contraction was determined...

  10. Itopride in the treatment of functional dyspepsia in Chinese patients: a prospective, multicentre, post-marketing observational study.

    Science.gov (United States)

    Sun, Jing; Yuan, Yao-Zong; Holtmann, Gerald

    2011-12-01

    Prokinetic agents are commonly used in the symptomatic treatment of functional dyspepsia (FD). Safety or efficacy issues associated with the use of available prokinetics, such as metoclopramide, domperidone, cisapride and mosapride, mean there is a need for an effective and well tolerated prokinetic agent. Itopride is a novel prokinetic agent with a dual mode of action, good safety profile and documented efficacy in placebo-controlled trials. The objective of this study was to assess the effectiveness and safety of itopride in the management of FD. This was a prospective, multicentre, post-marketing observational study carried out in private outpatient clinics throughout China. The study included patients with symptomatic FD aged ≥18 years. Patients were prescribed itopride 50 mg three times daily before meals for 4 weeks, after which there was a 2-week follow-up period during which they did not take itopride. Effectiveness and tolerability data obtained from patients who completed 4 weeks of therapy were analysed. The treatment response rate after 4 weeks was measured by patient global assessment; scores at the end of treatment were compared with baseline scores. Response rate based on symptom scoring was also measured after 4 weeks, with an effective treatment being defined as a symptom improvement of ≥50%. In total, 587 patients with FD were enrolled. The mean ± SD difference in the total symptom score before and after the 4-week treatment period was -5.62 ± 3.27, corresponding to a 69.23 ± 26.53% reduction from baseline (p Itopride was an effective and well tolerated drug in the management of FD in this patient population.

  11. Small intestinal bacterial overgrowth in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Saara Rawn

    2017-01-01

    Full Text Available Small intestinal bacterial overgrowth (SIBO is common in patients with systemic sclerosis (SSc yet often goes underrecognized in clinical practice. In patients with SSc, untreated SIBO may result in marked morbidity and possible mortality. The pathogenesis of SIBO is multifactorial and relates to immune dysregulation, vasculopathy, and dysmotility. This article reviews various diagnostic approaches and therapeutic options for SIBO. Treatment modalities mainly include prokinetics, probiotics, and antibiotics.

  12. Randomised clinical trial of Levonantradol and Chlorpromazine in the prevention of radiotherapy-induced vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Lucraft, H H; Palmer, M K [Christie Hospital and Holt Radium Inst., Manchester (UK)

    1982-11-01

    Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 25 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial.

  13. Randomised clinical trial of Levonantradol and Chlorpromazine in the prevention of radiotherapy-induced vomiting

    International Nuclear Information System (INIS)

    Lucraft, H.H.; Palmer, M.K.

    1982-01-01

    Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 25 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial. (author)

  14. The incidence of anticipatory nausea and vomiting after repeat cycle chemotherapy: the effect of granisetron.

    Science.gov (United States)

    Aapro, M. S.; Kirchner, V.; Terrey, J. P.

    1994-01-01

    Anticipatory nausea and vomiting (ANV) after repeated cycles of cytotoxic chemotherapy is thought to be a conditioned response to a conditioning stimulus. Good control of acute and delayed emesis may result in a lower incidence of ANV. We have analysed data from 574 chemotherapy patients who received granisetron as their antiemetic treatment during repeat cycle chemotherapy. Per treatment cycle, less than 10% of patients displayed symptoms of anticipatory nausea and 2% or less had symptoms of anticipatory vomiting. It is concluded that the use of granisetron as an antiemetic during the acute phase of chemotherapy may result in a lower incidence of ANV in patients undergoing repeat cycle chemotherapy. PMID:8180031

  15. Pathophysiology and treatment of patients with globus sensation ―from the viewpoint of esophageal motility dysfunction―

    Science.gov (United States)

    Manabe, Noriaki; Tsutsui, Hideaki; Kusunoki, Hiroaki; Hata, Jiro; Haruma, Ken

    2014-01-01

    "Globus sensation" is often described as the sensation of a lump in the throat associated with dry swallowing or the need for dry swallowing, which disappears completely during eating or drinking and for which no organic cause can be established. Due to the uncertain etiology of "globus sensation", it remains difficult to establish standard treatment strategies for affected patients. Lately most attention has been focused on gastroesophageal reflux disease and several reports have indicated that there is a close relationship between esophageal acid reflux and globus sensation. Nowadays, empirical therapy with a high dose of a proton pump inhibitor (PPI) is considered to be indicated for patients with globus sensation, after excluding organic diseases such as pharyngeal cancer, Zenker's diverticulum, or thyroid enlargement. If patients are nonresponsive to PPI therapy, evaluation of esophageal motility should be done. In our recent study, 47.9% had abnormal esophageal motility, with the most common esophageal motility abnormality being an ineffective esophageal motility in PPI-resistant patients with globus sensation. This suggests that prokinetics alone or adding prokinetics to PPI should be the treatment to be considered, although few studies have investigated the efficacy of prokinetics in the treatment of patients with globus sensation. If patients without any esophageal motility dysfunctions are nonresponsive to PPI therapy, either cognitive-behavioral therapy, anti-depressants, or gabapentin could be helpful, although further well-designed, randomized controlled large-scale studies will be necessary to determine the effectiveness of each treatment strategy on patients with globus sensation. PMID:26081369

  16. What Is Psychiatry?

    Medline Plus

    Full Text Available ... used to treat psychotic symptoms (delusions and hallucinations), schizophrenia, bipolar disorder. Sedatives and anxiolytics – used to treat ... Personality Disorders Postpartum Depression Posttraumatic Stress Disorder (PTSD) Schizophrenia Sleep Disorders Somatic Symptom Disorder Specific Learning Disorder ...

  17. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

    NARCIS (Netherlands)

    Koch, Saskia B. J.; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2016-01-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single

  18. Journal of Pharmaceutical and Allied Sciences - Vol 10, No 2 (2013)

    African Journals Online (AJOL)

    Prescription pattern of anxiolytic drugs in burn patients: a case study of national orthopaedic hospital, Enugu, Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. ALE Uzondu, JO Okafor, 1822-1837 ...

  19. Sudan Journal of Medical Sciences - Vol 9, No 3 (2014)

    African Journals Online (AJOL)

    Anticonvulsant and Anxiolytic Properties of the Roots of Grewia bicolor in Rats · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. MI Shamoun, AH Mohamed, TM El-Hadiyah, 137-143 ...

  20. Author Details

    African Journals Online (AJOL)

    inflammatory properties of the leaf extracts of Hedranthera barteri in rats and mice. Abstract PDF · Vol 13, No 1 (2010) - Articles Antidepressant and Anxiolytic Potentials of Dichloromethane Fraction from Hedranthera barteri. Abstract PDF. ISSN: 1119- ...

  1. South African Medical Journal - Vol 47, No 4 (1973)

    African Journals Online (AJOL)

    Evaluation of Lorazepam as an Anxiolytic Agent in Psychiatric Practice ... Cushing's Syndrome tumour and bilateral hyperplasia · EMAIL FREE FULL TEXT EMAIL .... and Imipramine Hydrochloride in the Treatment of Non-Psychotic Depression ...

  2. Serotonin and decision making processes.

    NARCIS (Netherlands)

    Homberg, J.R.

    2012-01-01

    Serotonin (5-HT) is an important player in decision making. Serotonergic antidepressant, anxiolytic and antipsychotic drugs are extensively used in the treatment of neuropsychiatric disorders characterized by impaired decision making, and exert both beneficial and harmful effects in patients.

  3. Neuropharmacological effects of Nigerian honey in mice | Akanmu ...

    African Journals Online (AJOL)

    10%, 20% and 40%V/v, p.o.) from three geographical locations of Nigeria using the following behavioral models: Novelty-induced behaviors (NIB), learning and memory, pentobarbital-induced hypnosis, anxiolytic, anticonvulsant, analgesic and ...

  4. 21 CFR 336.80 - Professional labeling.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Professional labeling. 336.80 Section 336.80 Food... HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 336.80 Professional labeling. The labeling provided to health professionals (but not to the general public) may contain the...

  5. The nutritional management of a patient with acute myeloid leukaemia

    African Journals Online (AJOL)

    The blood tests commonly show an elevated white blood cell ... history of alcohol abuse (he had stopped drinking four years earlier). Two of his ... a Serratia urinary tract infection. He also .... The patient was on antiemetic medication to relieve the nausea ..... the main site for L-glutamine synthesis and storage.17 Glutamine.

  6. 21 CFR 522.1962 - Promazine hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... for tetanus. (B) For use as a tranquilizer and preanesthetic. (iii) Limitations. Not for use in horses... (c)(1)(iii) of this section. (c) Conditions of use—(1) Horses—(i) Amount—(A) 0.2 to 0.5 milligrams... conjunction with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming...

  7. Structural basis of ligand recognition in 5-HT(3) receptors

    NARCIS (Netherlands)

    Kesters, D.; Thompson, A.J.; Brams, M.; van Elk, R.; Spurny, R.; Geitmann, M.; Villalgordo, J.M.; Guskov, A.; Danielson, U.H.; Lummis, S.C.R.; Smit, A.B.; Ulens, C.

    2013-01-01

    The 5-HT 3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist

  8. 5-HT3-receptorantagonisten als vervangers van metoclopramide en domperidon

    NARCIS (Netherlands)

    Mouch, Ikrame; Brouwers, J R B J; van 't Riet, E; Nieboer, Peter; Otten, Marten H; Jansman, Frank G A

    2016-01-01

    OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period

  9. Development and Validation of a New RP-HPLC Method for the ...

    African Journals Online (AJOL)

    Erah

    cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human positron emission tomography (PET) studies with APT have shown that it crosses the blood brain barrier and occupies brain NK 1 receptors [2]. Animal and human studies show that APT augments the antiemetic activity of the 5-HT3.

  10. Triage and Treatment of Combined Injury in Mass Casualty Situations

    Science.gov (United States)

    1996-11-01

    NOTES 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 21 19a. NAME OF...within 24-48 hours after CI. Antiemetic drugs, such as Ondansetron, Granisetron , Dimetcarb or Dixaphen, are useful for nausea and vomiting removal

  11. TRIAGE of Irradiated Personnel

    Science.gov (United States)

    1996-09-25

    DISTRIBUTION/AVAILABILITY STATEMENT APUBLIC RELEASE , 13. SUPPLEMENTARY NOTES 14. ABSTRACT See Report 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF...4510). Under draft STANAG 4511, multiple pro- phylactic antiemetic medications and regimens were evaluated prior to adoption of granisetron . Two drugs...exceeded the criteria (shown below), granisetron and ondansetron. The former was adopted due to a better technical profile and the operational

  12. Acute gastroenteritis: from guidelines to real life

    Directory of Open Access Journals (Sweden)

    Chung M Chow

    2010-07-01

    Full Text Available Chung M Chow1, Alexander KC Leung2, Kam L Hon11Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China; 2Department of Pediatrics, The University of Calgary, Calgary, Alberta, CanadaAbstract: Acute gastroenteritis is a very common disease. It causes significant mortality in developing countries and significant economic burden to developed countries. Viruses are ­responsible for approximately 70% of episodes of acute gastroenteritis in children and rotavirus is one of the best studied of these viruses. Oral rehydration therapy is as effective as i­ntravenous therapy in treating mild to moderate dehydration in acute gastroenteritis and is strongly r­ecommended as the first line therapy. However, the oral rehydration solution is described as an underused simple solution. Vomiting is one of the main reasons to explain the underuse of oral rehydration therapy. Antiemetics are not routinely recommended in treating acute gastroenteritis, though they are still commonly prescribed. Ondansetron is one of the best studied antiemetics and its role in enhancing the compliance of oral rehydration therapy and decreasing the rate of hospitalization has been proved recently. The guidelines regarding the recommendation on antiemetics have been changed according to the evidence of these recent studies.Keywords: gastroenteritis, vomiting, antiemetic, ondansetron, rotavirus, oral rehydration therapy, intravenous therapy, guideline

  13. 2016 updated MASCC/ESMO consensus recommendations

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Hesketh, Paul J

    2017-01-01

    PURPOSE: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out. METHODS: A systematic literature search using PubMed from Janua...

  14. Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Raafat Abdel-Malek

    2017-09-01

    Conclusion: This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.

  15. Browse Title Index

    African Journals Online (AJOL)

    Vol 7, No 17 (2008), Anti-emetic activity of Grewia lasiodiscus root extract and fractions, Abstract PDF. AY Tijani, SE Okhale, FE Oga, SZ Tags, OA Salawu, BA Chindo. Vol 13, No 27 (2014), Antifouling potential of seaweed, sponge and cashew nut oil extracts against biofilm bacteria and green mussel Perna viridis from ...

  16. Transdermal hyoscine induced unilateral mydriasis.

    LENUS (Irish Health Repository)

    Hannon, Breffni

    2012-03-20

    The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

  17. Radiogenic hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Rey, G; Woellgens, P; Haase, W [Katharinenhospital, Stuttgart (F.R. Germany). Strahlenklinik

    1976-08-01

    The article is about a patient who developed hepatitis after post-operative radiotherapy of a hypernephroma on the right side with /sup 60/Co ..gamma.. radiation. The scintigraph showed a normal-sized liver with parenchymal defects. Therapy consisted of anti-emetics and vitamin preparations.

  18. A Controlled Study Using Acupuncture as an Adjuvant to Treat Chemotherpay-Induced Nausea and Vomiting

    National Research Council Canada - National Science Library

    Lao, Lixing

    2000-01-01

    ...) on nausea and vomiting induced by chemotherapy in breast cancer patients. The primary aim of this study is to evaluate the usefulness of HA as an adjuvant on N/v in chemotherapy patients who do not respond to conventional antiemetics...

  19. Metabolism of clebopride in vitro. Mass spectrometry and identification of products of amide hydrolysis and N-debenzylation.

    Science.gov (United States)

    Huizing, G; Beckett, A H; Segura, J; Bakke, O M

    1980-03-01

    1. Electron impact and field desorption mass spectrometry is described and discussed for clebopride, a newly developed benzamide with anti-emetic and anti-dopaminergic properties, and for some related compounds. 2. When clebopride was incubated with liver homogenates of rabbits, 4-amino-5-chloro-2-methoxybenzoic acid and N-(4'-piperidyl)-4-amino-5-chloro-2-methoxybenzamide were identified as metabolites.

  20. Clinical and Financial Effects of Psychoeducational Care Provided by Staff Nurses to Adult Surgical Patients in the Post-DRG Environment.

    Science.gov (United States)

    Devine, Elizabeth C.; And Others

    1988-01-01

    A three-hour, two-stage workshop for staff nurses on providing education and psychological support to 148 patients who had abdominal surgery. After the workshop the patients used fewer sedatives or antiemetics, fewer hypnotics, and were discharged from the hospital on the average half a day sooner. (Author/BJV)

  1. Chemotherapy-induced nausea, vomiting, and fatigue - the role of individual differences related to sensory perception and autonomic reactivity

    DEFF Research Database (Denmark)

    Zachariae, Robert; Paulsen, Kim; Mehlsen, Mimi Yung

    2007-01-01

    BACKGROUND: In spite of antiemetics, postchemotherapy side effects continue to be common and may affect compliance to cancer treatment. Among the known factors associated with increased symptom severity are: younger age, treatment toxicity, expected severity, and distress, but little is still kno...

  2. POSTOPERATIVE NAUSEA AND VOMITING | Yusufu | Annals of ...

    African Journals Online (AJOL)

    Antiemetics, acupuncture and other drugs are used to prevent and treat postoperative nausea and vomiting. Those that manage patients in the postoperative period should endeavour to make postoperative nausea and vomiting as unacceptable as postoperative pain. Key words: Postoperative, Nausea, Vomiting, Narcotics, ...

  3. Important interaction between mirtazapine and ondansetron

    African Journals Online (AJOL)

    We report an unexpected interaction between the antidepressant mirtazapine and the antiemetic ondansetron in a 72 year old patient, weighing 68 kg, with a height of 173 cm. The patient, who gave his informed consent for anonymous publication, underwent electro-convulsive therapy (ECT), using a Thymatron System II, ...

  4. Hyperemesis gravidarum

    DEFF Research Database (Denmark)

    Schouenborg, L O; Honnens de Lichtenberg, M; Djursing, H

    1992-01-01

    of the pregnancy usually runs a normal course. All of the forms of treatment are dominated by the tendency to spontaneous remission and great placebo effect. Antihistamines, antiemetics, ginger, change of environment, hypnotherapy and psychotherapy appear to be the best forms of treatment....

  5. Prevention of acute chemotherapy-induced nausea and vomiting: the role of palonosetron

    Directory of Open Access Journals (Sweden)

    Emilio Bajetta

    2009-08-01

    Full Text Available Emilio Bajetta, Sara Pusceddu, Valentina Guadalupi, Monika Ducceschi, Luigi CelioMedical Oncology Unit 2, Fondazione IRCCS “Istituto Nazionale dei Tumori”, Milan, ItalyAbstract: Prevention of nausea and vomiting is the main goal of antiemetic treatment in cancer patients scheduled to receive chemotherapy. To prevent acute emesis, antiemetics should be administered just before chemotherapy and patients should be protected for up to 24 hours after chemotherapy initiation. The emetogenic potential of chemotherapeutic agents guides clinicians towards the most appropriate antiemetic prophylaxis. Current guidelines recommend the use of 5-HT3 receptor antagonist (RA either alone or in combination with dexamethasone and/or a neurokinin-1 RA both in the acute and delayed phases. The second-generation 5-HT3RA palonosetron exhibits a longer half-life and a higher binding affinity than older antagonists. Palonosetron has been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV in patients scheduled to receive either moderately (MEC or highly emetogenic chemotherapy (HEC and for the prevention of delayed CINV in patients receiving MEC. The present review will discuss the role of palonosetron in the prevention of acute CINV.Keywords: antiemetics, chemotherapy, nausea, vomiting, serotonin-receptor antagonists, palonosetron

  6. Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

    International Nuclear Information System (INIS)

    King, G.L.; Landauer, M.R.

    1990-01-01

    The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways

  7. Cost-effectiveness of an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer in the UK

    Directory of Open Access Journals (Sweden)

    Humphreys S

    2013-08-01

    Full Text Available Samantha Humphreys,1 James Pellissier,2 Alison Jones3 1Market Access Department, Merck Sharp and Dohme Ltd, Hoddesdon, Hertfordshire, UK; 2Health Economic Statistics, Merck Research Laboratories, Upper Gwynedd, PA, USA; 3Department of Medical Oncology, University College Hospital, London, UK Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV remains an important goal for patients receiving chemotherapy. The objective of this study was to define, from the UK payer perspective, the cost-effectiveness of an antiemetic regimen using aprepitant, a selective neurokinin-1 receptor antagonist, for patients receiving chemotherapy for breast cancer. Methods: A decision-analytic model was developed to compare an aprepitant regimen (aprepitant, ondansetron, and dexamethasone with a standard UK antiemetic regimen (ondansetron, dexamethasone, and metoclopramide for expected costs and health outcomes after single-day adjuvant chemotherapy for breast cancer. The model was populated with results from patients with breast cancer participating in a randomized trial of CINV preventative therapy for cycle 1 of single-day chemotherapy. Results: During 5 days after chemotherapy, 64% of patients receiving the aprepitant regimen and 47% of those receiving the UK comparator regimen had a complete response to antiemetic therapy (no emesis and no rescue antiemetic therapy. A mean of £37.11 (78% of the cost of aprepitant was offset by reduced health care resource utilization costs. The predicted gain in quality-adjusted lifeyears (QALYs with the aprepitant regimen was 0.0048. The incremental cost effectiveness ratio (ICER with aprepitant, relative to the UK comparator, was £10,847/QALY, which is well below the threshold commonly accepted in the UK of £20,000–£30,000/QALY. Conclusion: The results of this study suggest that aprepitant is cost-effective for preventing CINV associated with chemotherapy for patients with breast cancer in the UK health

  8. Radiotherapy-induced emesis. An overview

    International Nuclear Information System (INIS)

    Feyer, P.; Buchali, A.; Hinkelbein, M.; Budach, V.; Zimmermann, J.S.; Titlbach, O.J.

    1998-01-01

    Background: A significant number of patients receiving radiotherapy experience the distressing side effects of emesis and nausea. These symptoms are some of the most distressing problems for the patients influencing their quality of life. Methods: International study results concerning radiotherapy-induced emesis are demonstrated. A German multicenter questionnaire examining the strategies to prevent or to treat radiotherapy-induced nausea and emesis is presented. An international analysis concerning incidence of emesis and nausea in fractionated radiotherapy patients is discussed. Finally the consensus of the consensus conference on antiemetic therapy from the Perugia International Cancer Conference V is introduced. Results: Untreated emesis can lead to complications like electrolyte disorders, dehydration, metabolic disturbances and nutrition problems with weight loss. Prophylactic antiemetics are often given to patients receiving single high-dose radiotherapy to the abdomen. A survey has revealed that antiemetic prophylaxis is not routinely offered to the patients receiving fractionated radiotherapy. However, there is a need for an effective treatment of emesis for use in this group of patients, too. In 20% of patients nausea and emesis can cause a treatment interruption because of an inadequate control of symptoms. Like in chemotherapy strategies there exist high, moderate, and low emetogenic treatment regimens in radiotherapy as well. The most emetogenic potential has the total body irradiation followed by radiotherapy to the abdomen. Radiotherapy induced emesis can be treated effectively with conventional antiemetics up to 50%. Conclusions: Studies with total body irradiation, fractionated treatment and high-dose single exposures have cleary demonstrated the value of 5-HT3-receptor antagonist antiemetics. There is a response between 60 and 97%. There is no difference in the efficacy of the different 5-HT3-antagonists. High-risk patients should be prophylactic

  9. Comparison of anxiety between smokers and nonsmokers with acute myocardial infarction.

    Science.gov (United States)

    Sheahan, Sharon L; Rayens, Mary K; An, Kyungeh; Riegel, Barbara; McKinley, Sharon; Doering, Lynn; Garvin, Bonnie J; Moser, Debra K

    2006-11-01

    Increased anxiety correlates with increased complications after acute myocardial infarction. Anxiety levels and use of anxiolytic agents have not been compared between smokers and nonsmokers hospitalized because of acute myocardial infarction. To compare anxiety level, sociodemographic factors, and clinical variables between smokers and nonsmokers hospitalized with acute myocardial infarction and to examine predictors of use of beta-blockers and anxiolytic agents among smokers and nonsmokers. Secondary data analysis of a prospective multisite study on anxiety in 181 smokers and 351 nonsmokers with acute myocardial infarction. Anxiety was measured by using the State Trait Anxiety Inventory and the anxiety subscale of the Basic Symptom Inventory within 72 hours of admission. Smokers reported higher anxiety levels than nonsmokers reported on both anxiety scales. Female smokers reported the highest anxiety and peak pain levels of all, yet women were the least likely to receive anxiolytic agents. Smoking status was not a predictor for anxiety level when sex, peak pain, use of beta-blockers in the hospital, and age were controlled for. However, smokers were twice as likely as nonsmokers to receive an anxiolytic agent and 60% more likely to receive a beta-blocker in the emergency department, and smokers were 80% more likely than nonsmokers to receive an anxiolytic agent during hospitalization when these variables were controlled. Older female smokers are at risk for complications because they are older than their male counterparts and less likely to receive beta-blockers and antianxiety medications in the emergency department.

  10. [Differentiation therapy for non-acidic gastroesophageal reflux disease].

    Science.gov (United States)

    Lishchuk, N B; Simanenkov, V I; Tikhonov, S V

    2017-01-01

    To investigate the clinical and pathogenetic features of the non-acidic types of gastroesophageal reflux disease (GERD) and to evaluate the impact of combined therapy versus monotherapy on the course of this disease. The investigation enrolled 62 patients with non-acidic GERD. The follow-up period was 6 weeks. The patients were divided into 2 groups: 1) weakly acidic gastroesophageal refluxes (GER); 2) weakly alkaline GER. Then each group was distributed, thus making up 4 groups: 1) 19 patients with weakly acidic GER who received monotherapy with rabeprazole 20 mg/day; 2) 21 patients with weakly acidic GER had combined therapy with rabeprazole 20 mg and itopride; 3) 8 patients with weakly alkaline GER who received ursodeoxycholic acid (UDCA) monotherapy; and 4) 14 patients with weakly alkaline GER who had combined therapy with UDCA and itopride, The clinical symptoms of the disease, the endoscopic pattern of the upper gastrointestinal tract (GIT) mucosa, histological changes in the esophageal and gastric mucosa, and the results of 24-hour impedance pH monitoring were assessed over time. During differentiation therapy, the majority of patients reported positive clinical changes and an improved or unchanged endoscopic pattern. Assessment of impedance pH monitoring results revealed decreases in the overall number of GERs, the presence of a bolus in the esophagus, and the number of proximal refluxes. These changes were noted not only in patients taking proton pump inhibitors (PPIs), but also in those treated with UDCA monotherapy or combined PPI and prokinetic therapy. A differentiated approach to non-acidic GER treatment contributes to its efficiency. Adding the prokinetic itomed (itopride hydrochloride) to PPI therapy in a patient with weakly acidic GER enhances the efficiency of treatment, by positively affecting upper GIT motility. The mainstay of therapy for GERD with a predominance of weakly alkaline refluxes is UDCA, the combination of the latter and the

  11. Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms.

    Science.gov (United States)

    White, Paul F; Tang, Jun; Song, Dajun; Coleman, Jayne E; Wender, Ronald H; Ogunnaike, Babatunde; Sloninsky, Alexander; Kapu, Rajani; Shah, Mary; Webb, Tom

    2007-01-01

    Given the controversy regarding the use of droperidol and the high cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a prophylactic antiemetic would be desirable. We designed two parallel, randomized, double-blind sham and placebo-controlled studies to compare the early and late antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS) 1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic prophylaxis as part of a multimodal regimen in "at risk" surgical populations. A total of 150 patients undergoing major laparoscopic (n = 80) or plastic (n = 70) surgery procedures received either an active TDS patch (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before entering the operating room. All patients received a standardized general anesthetic technique. A second study medication was administered in a 2-mL numbered syringe containing either saline (for the two active TDS groups), droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was administered IV near the end of the procedure. The occurrence of postoperative nausea and vomiting/retching, need for rescue antiemetics, and the complete response rates (i.e., absence of protracted nausea or repeated episodes of emesis requiring antiemetic rescue medication) was reported. In addition, complaints of visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72 h after surgery. There were no significant differences in any of the emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and ondansetron groups in the first 72 h after surgery. The complete response rates varied from 41% to 51%, and did not significantly differ among the treatment groups. The overall incidence of dry mouth was significantly more frequent in the TDS groups than in the droperidol and ondansetron groups (21% vs 3%). Premedication with TDS was as effective as droperidol (1.25 mg) or ondansetron (4

  12. Endoscopic management of acute peptic ulcer bleeding.

    Science.gov (United States)

    Lu, Yidan; Chen, Yen-I; Barkun, Alan

    2014-12-01

    This review discusses the indications, technical aspects, and comparative effectiveness of the endoscopic treatment of upper gastrointestinal bleeding caused by peptic ulcer. Pre-endoscopic considerations, such as the use of prokinetics and timing of endoscopy, are reviewed. In addition, this article examines aspects of postendoscopic care such as the effectiveness, dosing, and duration of postendoscopic proton-pump inhibitors, Helicobacter pylori testing, and benefits of treatment in terms of preventing rebleeding; and the use of nonsteroidal anti-inflammatory drugs, antiplatelet agents, and oral anticoagulants, including direct thrombin and Xa inhibitors, following acute peptic ulcer bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Plant-based medicines for anxiety disorders, Part 1: a review of preclinical studies.

    Science.gov (United States)

    Sarris, Jerome; McIntyre, Erica; Camfield, David A

    2013-03-01

    Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. This article (part 1) reviews herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In part 2, we review herbal medicines for which there have been clinical investigations for anxiolytic activity. An open-ended, language-restricted (English) search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) using specific search criteria to identify herbal medicines that have been investigated for anxiolytic activity. This search of the literature revealed 1,525 papers, from which 53 herbal medicines were included in the full review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed in part 2), with another 32 having solely preclinical studies (reviewed here in part 1). Preclinical evidence of anxiolytic activity (without human clinical trials) was found for Albizia julibrissin, Sonchus oleraceus, Uncaria rhynchophylla, Stachys lavandulifolia, Cecropia glazioui, Magnolia spp., Eschscholzia californica, Erythrina spp., Annona spp., Rubus brasiliensis, Apocynum venetum, Nauclea latifolia, Equisetum arvense, Tilia spp., Securidaca longepedunculata, Achillea millefolium, Leea indica, Juncus effusus, Coriandrum sativum, Eurycoma longifolia, Turnera diffusa, Euphorbia hirta, Justicia spp., Crocus sativus, Aloysia polystachya, Albies pindrow, Casimiroa edulis, Davilla rugosa, Gastrodia elata, Sphaerathus indicus, Zizyphus jujuba and Panax ginseng. Common mechanisms of action for the majority of botanicals reviewed primarily involve GABA, either via direct receptor binding or ionic channel or cell membrane modulation; GABA transaminase

  14. Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02).

    Science.gov (United States)

    Ohnishi, Shunsuke; Watari, Hidemichi; Kanno, Maki; Ohba, Yoko; Takeuchi, Satoshi; Miyaji, Tempei; Oyamada, Shunsuke; Nomura, Eiji; Kato, Hidenori; Sugiyama, Toru; Asaka, Masahiro; Sakuragi, Noriaki; Yamaguchi, Takuhiro; Uezono, Yasuhito; Iwase, Satoru

    2017-09-01

    Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0-13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0-120 hours). Two-tailed panorexia. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  15. Sleep Quality Effects Recovery After Total Knee Arthroplasty (TKA)--A Randomized, Double-Blind, Controlled Study.

    Science.gov (United States)

    Gong, Long; Wang, ZhenHu; Fan, Dong

    2015-11-01

    This study examined the effects of sleep quality on early recovery after total knee arthroplasty. A total of 148 patients were randomized 1:1 to receive either zolpidem or placebo for 2 weeks. VAS pain scores (rest, ambulation and night), range of motion (ROM), total amount of opioid analgesics and antiemetics taken, postoperative nausea and vomiting (PONV), sleep efficacy and satisfaction were recorded. It was found that patients taking zolpidem achieved greater improvement in quality of life and reported better satisfaction. Patients in the intervention group had lower pain score and took less antiemetics. Moreover, a significant correlation between sleep quality and ROM was detected. These results demonstrated that improved sleep quality is beneficial to patients' post-TKA recovery. Copyright © 2015. Published by Elsevier Inc.

  16. Chemotherapy in patients with hepatic failure

    International Nuclear Information System (INIS)

    Roldán, G.; Sosa, A.

    2004-01-01

    The toxicity of chemotherapy in the liver may manifest as hepatocyte dysfunction with chemical hepatitis, veno-occlusive disease or chronic fibrosis. The hepatocyte dysfunction is caused by direct effect of the drug or its metabolites evidencing by increased bilirubin and liver enzymes (Sgot, SGPT). Prolonged effect leads to cholestasis and fatty infiltration. This dysfunction is concomitant enhanced by viral infection, liver metastases and other drugs as antiemetics. The vast majority of the indicated drugs in a cancer patient, cytostatics, antiemetics, analgésios, anticonvulsants, etc, are metabolized in the liver. The evidence of abnormal hepatocyte function in a patient in which involves chemotherapy raises the need for dose modification indicated and / or discontinuation. The aim of this paper is to review existing information on the use of cytostatics in cancer patients with hepatic impairment, classifying drugs according to their potential hepato toxicity and recommended dose modification in patients with hepatic dysfunction

  17. The effect of aromatherapy on postoperative nausea in women undergoing surgical procedures.

    Science.gov (United States)

    Ferruggiari, Luisa; Ragione, Barbara; Rich, Ellen R; Lock, Kathleen

    2012-08-01

    Postoperative nausea and vomiting (PONV) is a common source of patient discomfort and decreased satisfaction. Aromatherapy has been identified as a complementary modality for the prevention and management of PONV. The purpose of this study was to assess the effect of aromatherapy on the severity of postoperative nausea (PON) in women undergoing surgical procedures in the postanesthesia care unit. Women complaining of PON received traditional antiemetics, inhalation of peppermint oil, or saline vapor. A visual analog scale was used to rate nausea at the first complaint; at 5 minutes after intervention; and, if nausea persisted, at 10 minutes after intervention. At both 5 and 10 minutes, statistical analysis showed no significant differences between intervention and nausea rating. Obtaining eligible subjects was challenging. Although many women consented, most received intraoperative antiemetics and did not report nausea postoperatively. Copyright © 2012 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  18. Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting

    DEFF Research Database (Denmark)

    Ruhlmann, Christina H; Herrstedt, Jørn

    2011-01-01

    INTRODUCTION: Aprepitant is the only neurokinin (NK(1)) receptor antagonist (RA) approved for prevention of chemotherapy-induced nausea and vomiting (CINV). Aprepitant is co-administered with a 5-HT(3) RA and a corticosteroid. Although aprepitant is safe, in most clinical settings potential drug......A4, MK-0869, neurokinin(1) receptor antagonist, safety and tolerability. EXPERT OPINION: The recommended antiemetic regimen of aprepitant, a 5-HT(3) RA and a corticosteroid is safe. The combination of aprepitant, a 5-HT(3) RA and dexamethasone is now the gold standard of antiemetic treatment...... in prevention of CINV induced by HEC, or by the combination of an anthracycline and cyclophosphamide. The intravenous formulation of aprepitant used as a single dose is expected to be of benefit to cancer patients....

  19. Neurokinin NK1 and NK3 receptors as targets for drugs to treat gastrointestinal motility disorders and pain

    OpenAIRE

    Sanger, Gareth J

    2004-01-01

    NK1 and NK3 receptors do not appear to play significant roles in normal GI functions, but both may be involved in defensive or pathological processes. NK1 receptor antagonists are antiemetic, operating via vagal sensory and motor systems, so there is a need to study their effects on other gastro-vagal functions thought to play roles in functional bowel disorder's. Interactions between NK1 receptors and enteric nonadrenergic, noncholinergic motorneurones suggest a need to explore the role of t...

  20. Anti emetic effect of 5HT3 receptor antagonists in macaques exposed to a neutron-gamma radiation

    International Nuclear Information System (INIS)

    Agay, D.; Martin, C.; Martin, S.; Roman, V.; Fatome, M.

    1994-01-01

    Ondansetron and granisetron were tested as antiemetics in cynomolgus macaques weighing 4 kg and submitted to a neutron-gamma irradiation with a high neutronic component. Compounds were delivered by oral way, each administration dose being 4 mg of ondansetron or 1 mg of granisetron. The effect was complete when were delivered before and after the irradiation. It was incomplete when there was a single administration be fore or after the exposure. No adverse side-effects were noted. (author)

  1. Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

    Science.gov (United States)

    Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo

    2013-11-01

    We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

  2. Double-blind comparison of granisetron, promethazine, or a combination of both for the prevention of postoperative nausea and vomiting in females undergoing outpatient laparoscopies.

    Science.gov (United States)

    Gan, Tong J; Candiotti, Keith A; Klein, Stephen M; Rodriguez, Yiliam; Nielsen, Karen C; White, William D; Habib, Ashraf S

    2009-11-01

    Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common problems after surgery. Prophylactic combination antiemetic therapy is recommended for patients at high risk for developing PONV and PDNV. Granisetron, a serotonin antagonist, is an effective antiemetic that is devoid of sedative side effect. Although promethazine is effective, commonly used doses are associated with sedation. This study investigates the combination of low doses of granisetron and promethazine for the prevention of PONV. Women undergoing ambulatory gynecological laparoscopy were enrolled. A standard general anesthetic regimen was prescribed. Fifteen minutes before the expected end of surgery, the patients were randomly assigned to receive granisetron 0.1 mg iv, promethazine 6.25 mg iv, or a combination of the two drugs. Prophylaxis with oral promethazine 12.5 mg, granisetron 1 mg, or both was started in the respective groups 12 hr after the end of surgery and continued every 12 hr until postoperative day 3 (a total of five oral doses). The following outcomes were recorded: total response rate (defined as no vomiting, no more than mild nausea, and no use of rescue antiemetic); incidence of nausea, vomiting, and use of rescue antiemetics; severity of nausea; patient activity level; and patient satisfaction with PONV management. Patients in the combination group had a higher total response rate at 6, 24, 48, and 72 hr after surgery compared with those who received promethazine alone (at 24 hr, Combination 69.6%, Promethazine 36.2%, Granisetron 53.3%; P = 0.0079). The maximum nausea scores were also lower in the combination group at 6, 24, 48, and 72 hr (Combination 1.7 +/- 2.2, Promethazine 4.0 +/- 3.6, Granisetron 3.1 +/- 3.2 at 24 hr; P granisetron and promethazine combination was more effective in reducing PONV and PDNV than promethazine monotherapy. The combination also reduced the severity of nausea.

  3. The effect of granisetron dexamethasone combination on postoperative nausea and vomiting in gynecological operations

    Directory of Open Access Journals (Sweden)

    Ziya Kaya

    2010-06-01

    Full Text Available Objectives: Postoperative nausea and vomiting (PONV is one of the most frequent adverse effects of anesthesia. PONV postpones hospital stays and also delays recover and getting better, of the patients. The objective of the current study is to compare efficacy of prophylactic granisetron(40 μ/kg + dexamethasone (4 mg combination against PONV in different anesthesia models.Materials and Methods: 72 patients with an age range of 18-72 years and ASA 1 or 2 were enrolled in the present study. The patients were assigned as group 1 propofol-remifentanil (P-R, group 2 propofol- nitrous oxide (P-N2O, group 3 sevoflurane- nitrous oxide (S-N2O and group 4 sevoflurane-remifentanyl-air (S-R+H. Inductions of the patients in all groups were made with intravenous 2-3 mg/kg propofol, 1μ/kg remifentanil and 0.2 mg/kg cis-atracurium. 4 mg of dexamethasone by bolus and 40 μ/kg of granisetron by infusion were administered to the patients in all groups after induction. During the last 10 minutes of the operation, 1mg/kg tramadol was administered.Postoperative nausea and vomiting, VAS scores, and additional antiemetic needs were recorded during postoperative 48 hours.Results: Postoperative 48 hours follow up revealed that PONV was seen 27%, 16%, 38%, 48% frequencies in (P+R, (P+ N2O, (S+ N2O, (S+R+H groups, respectively.While antiemetic requirement was not observed in (P+ N2O and (S+ N2O groups, the patients in (P+R and (S+R+H groups needed additional antiemetic drugs with a frequency of 5.5% and 11% respectively.Conclusion: Granisetron, dexamethasone combination in different anesthetic models did not reveal significant difference in terms of postoperative nausea, vomiting, and additional antiemetic usage.

  4. Treatment of established postoperative nausea and vomiting: a quantitative systematic review

    Directory of Open Access Journals (Sweden)

    Tramèr Martin R

    2001-10-01

    Full Text Available Abstract Background The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV is poorly understood. Methods Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000 for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. Results In seven trials (1,267 patients, 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809 had placebo controls. Dolasetron 12.5–100 mg, granisetron 0.1–3 mg, tropisetron 0.5–5 mg, and ondansetron 1–8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%–30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK1 antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. Conclusions Of 100 vomiting surgical patients receiving a 5-HT3 receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed.

  5. Anti emetic effect of 5HT3 receptor antagonists in macaques exposed to a neutron-gamma radiation; Effet antiemetique d`antiserotoninergiques de type 3 chez le macaque soumis a une irradiation neutron-gamma

    Energy Technology Data Exchange (ETDEWEB)

    Agay, D.; Martin, C.; Martin, S.; Roman, V.; Fatome, M.

    1994-12-31

    Ondansetron and granisetron were tested as antiemetics in cynomolgus macaques weighing 4 kg and submitted to a neutron-gamma irradiation with a high neutronic component. Compounds were delivered by oral way, each administration dose being 4 mg of ondansetron or 1 mg of granisetron. The effect was complete when were delivered before and after the irradiation. It was incomplete when there was a single administration be fore or after the exposure. No adverse side-effects were noted. (author). 4 refs.

  6. Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group

    Science.gov (United States)

    2004-06-15

    STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY ...Assistance Medicine http://usuhs.mil U.S. Army www.nbc-med.org U.S. Department of Homeland Security Working Group on Radiological Dispersal Device...22. 97. Abbott B, Ippoliti C, Bruton J, Neumann J, Whaley R, Champlin R. Antiemetic efficacy of granisetron plus dexamethasone in bone marrow

  7. Medical Management of Radiological Casualties, Second Edition, Handbook

    Science.gov (United States)

    2003-04-01

    psychogenic vomit- ing that often results from stress and realistic fear reac- tions. Use of oral prophylactic antiemetics, such as granisetron (Kytril...covered prior to decontamination. Contaminated clothing should be carefully removed, placed in marked plastic bags, and re- moved to a secure location...clean treatment area to the dirty decontamination area). Key Principles Wind direction Security of the decontamination site Area control of the

  8. Medical Managment of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group

    Science.gov (United States)

    2004-06-15

    AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY ...Humanitarian Assistance Medicine http://usuhs.mil U.S. Army www.nbc-med.org U.S. Department of Homeland Security Working Group on Radiological Dispersal...2002:11-22. 97. Abbott B, Ippoliti C, Bruton J, Neumann J, Whaley R, Champlin R. Antiemetic efficacy of granisetron plus dexamethasone in bone marrow

  9. Acute Radiation Sickness Amelioration Analysis

    Science.gov (United States)

    1994-05-01

    Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron

  10. Medical Management of Radiological Casualties Handbook. First Edition

    Science.gov (United States)

    1999-12-01

    fear reac- tions. Use of oral prophylactic antiemetics, such as granisetron (Kytril®) and ondansetron (Zofran®), may be indicated in situations where...clothing should be carefully removed, placed in marked plastic bags, and re-Imoved to a secure location within a contaminated area. Bare skin and hair...the treatment area (i.e., wind blows from the clean treatment area to the dirty decontamination area). Key Principles • Wind direction " Security of the

  11. Combination of gabapentin and ramosetron for the prevention of postoperative nausea and vomiting after gynecologic laparoscopic surgery: a prospective randomized comparative study.

    Science.gov (United States)

    Kim, Kyung Mi; Huh, Jin; Lee, Soo Kyung; Park, Eun Young; Lee, Jung Min; Kim, Hyo Ju

    2017-05-19

    As a drug originally introduced for its anticonvulsant effects, gabapentin has been recently shown to be effective in the treatment of nausea and vomiting in various clinical settings. This study compared the antiemetic efficacy of oral gabapentin, intravenous ramosetron and gabapentin plus ramosetron in patients receiving fentanyl-based patient-controlled analgesia after laparoscopic gynecologic surgery. One hundred and thirty two patients undergoing laparoscopic gynecologic surgery under general anesthesia were allocated randomly into three groups: group G received 300 mg oral gabapentin 1 h before anesthesia, group R received 0.3 mg intravenous ramosetron at the end of surgery, and group GR received a combination of 300 mg oral gabapentin 1 h before anesthesia and 0.3 mg intravenous ramosetron at the end of surgery. Postoperative nausea, retching, vomiting, rescue antiemetic drug use, pain, rescue analgesic requirements and adverse effects were assessed at 0-2, 2-24 and 24-48 h after surgery. Postoperative nausea and vomiting (PONV) was defined as the presence of nausea, retching or vomiting. The incidence of complete response (no PONV and no rescue antiemetics up to 48 h postoperatively) was significantly higher in group GR (26/40, 65%) than group G (16/40, 40%; P = 0.025) and group R (18/44, 41%; P = 0.027), whereas there was no significant difference between group G and group R (P = 0.932). There were no significant between-group differences in the incidence of emetic episodes, use of rescue antiemetics, severe emesis, use of rescue analgesics or any adverse effects. Postoperative pain scores were also similar among groups. The combination with gabapentin and ramosetron is superior to either drug alone for prevention of PONV after laparoscopic gynecologic surgery. ClinicalTrials.gov NCT02617121 , registered November 25, 2015.

  12. Pengobatan infeksi parvovirus pada anjing

    Directory of Open Access Journals (Sweden)

    IKW Sardjana D Kusumawati

    2012-02-01

    Full Text Available Treatments of canine Parvovirus have already done to 22 dogs. There were 16 dogs, one month to one years of age and 6 dogs twoyears to seven years of age. The results of the theraphy, were ten dogs survived and twelve dogs died due to Parvovirus infection. Fluidtheraphy supported by antibiotic, antiemetic or antacids administrations were essential for Parvovirus infection in dogs. The recoveryrate of this dogs was 45%.

  13. Comparison of ramosetron with ondansetron for the prevention of post-operative nausea and vomiting in high-risk patients

    Directory of Open Access Journals (Sweden)

    Sandip Agarkar

    2015-01-01

    Full Text Available Background and Aims: Post-operative nausea and vomiting (PONV has an 80% incidence in high-risk patients. This is despite the availability of several antiemetic drugs. Selective 5-hydroxytryptamine type 3 (5-HT 3 receptor antagonists are considered first-line for prophylaxis, ondansetron being the most commonly used agent. Ramosetron, another selective 5-HT 3 receptor antagonist, is more potent and longer acting than ondansetron. This study was conducted to evaluate the antiemetic efficacy of ramosetron in comparison with ondansetron in patients at a high risk of PONV. Methods: This was a prospective randomised double-blind study carried out over a 6-month period in which 206 patients with at least two risk factors for PONV were randomised to receive ramosetron 0.3 mg or ondansetron 8 mg, 30 min before the end of surgery. The incidence of PONV, severity of nausea and need for rescue antiemetic were recorded over the next 24 h. Primary outcome was the incidence of PONV. Secondary outcomes included severity of nausea and need for rescue. The data were analysed using the Predictive Analytics Software (PASW, version 18: Chicago, IL, USA. Results: The incidence of PONV was found to be 35% in the ramosetron group as opposed to 43.7% in the ondansetron group (P = 0.199. Need for rescue antiemetic was 23.3% in the ramosetron group and 32% in the ondansetron group (P = 0.156 in the 24 h following surgery. Conclusion: Ramosetron 0.3 mg and ondansetron 8 mg were equally effective in reducing the incidence of PONV in high risk patients.

  14. Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

    OpenAIRE

    Dickman, Andrew; Bickerstaff, Matthew; Jackson, Richard; Schneider, Jennifer; Mason, Stephen; Ellershaw, John

    2017-01-01

    Background A continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer ref...

  15. Acupressure at acupoint P6 for prevention of postoperative nausea and vomiting: a randomised clinical trial

    DEFF Research Database (Denmark)

    Majholm, Birgitte; Møller, Ann M

    2011-01-01

    Postoperative nausea and vomiting causes discomfort in many patients despite both antiemetic prophylactics and improved anaesthetic techniques. Stimulation of acupoint P6 is described as an alternative method for prophylaxis of postoperative nausea and vomiting.In a randomised, double-blinded stu......, we aimed to investigate the effect of P6 acupoint stimulation on the incidence of postoperative nausea and vomiting within 24 h postoperatively with an acupressure wristband: Vital-Band....

  16. A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

    Science.gov (United States)

    Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

    2017-09-01

    The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. A Prospective Study of Postoperative Vomiting in Children Undergoing Different Surgical Procedures under General Anaesthesia

    Directory of Open Access Journals (Sweden)

    Jaya Choudhary

    2008-01-01

    Full Text Available To identify the risk factors associated with postoperative vomiting (POV in paediatric population undergoing common surgeries. The risk factors studied for association with POV were age> 5 years, female gender, previous history of POV/motion sickness, type of surgery and duration of anaesthesia> 45 min. A total of 100 ASA grade I and II patients of either sex aged between 2-12 years undergoing elective surgical procedures were screened for the study. All patients underwent similar anaesthe-sia protocol and received two antiemetic agents (ondansetron 0.05mg.kg-1 and dexamethasone 0.15mg.kg-1 in premedication. The patients were observed for 24 hours postoperatively for the incidence of vomiting, number of times rescue antiemetic given and any adverse reaction to antiemetic.Overall 34% patients (34/100 developed POV of which 26 had only one episode and 8 patients had 2 episodes during first 24 h. Incidence of POV was 13% (13/100 in first 4 h whereas it was 29% (29/100 in late postoperative period. In early post operative period, POV was not associated significantly with any predicted risk factors. However, age>5years, duration of anaesthesia>45 minutes and history of motion sickness/POV were significantly associated in late postoperative period(4-24h. Female gender and type of surgery were not associated with increased POV. The combination antiemetic effectively prevented POV in early postoperative period (0-4h only but not in late postoperative period(0-24h.

  18. Medical Surveillance Monthly Report (MSMR)

    Science.gov (United States)

    2016-11-01

    vomiting that can lead to dehydration, electrolyte and metabolic disturbances, and nutritional deficiencies.13-14 Hospitalization may be required...for correction of fluid and electrolyte imbalances as well as administra- tion of antiemetic medication and provision of nutritional counseling... Soccer (E007.5) 214 (2) Baseball (E007.3) 167 (2) aICD-9 activity code (E001–E030) was assigned to a total of 9,061 injury visits with an overexertion

  19. A prospective observational trial on emesis in radiotherapy: Analysis of 1020 patients recruited in 45 Italian radiation oncology centres

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; De Angelis, Verena; Pergolizzi, Stefano; Lupattelli, Marco; Frata, Paolo; Spagnesi, Stefano; Frisio, Maria Luisa; Mandoliti, Giovanni; Malinverni, Giuseppe; Trippa, Fabio; Fabbietti, Letizia; Parisi, Salvatore; Di Palma, Annamaria; De Vecchi, Pietro; De Renzis, Costantino; Giorgetti, Celestino; Bergami, Tiziano; Orecchia, Roberto; Portaluri, Maurizio; Signor, Marco

    2010-01-01

    Purpose: A prospective observational multicentre trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and to evaluate the use of antiemetic drugs in patients treated with radiotherapy or concomitant radio-chemotherapy. The application in clinical practice of the Multinational Association of Supportive Care in Cancer guidelines was also studied. Materials and methods: Forty-five Italian radiation oncology centres took part in this trial. The accrual lasted for 3 consecutive weeks and only patients starting radiotherapy or concomitant radio-chemotherapy in this period were enrolled. Evaluation was based on diary card filled in daily by patients during treatment and one week after stopping it. Diary card recorded the intensity of nausea/vomiting and prophylactic/symptomatic antiemetic drug prescriptions. Results: A total of 1020 patients entered into the trial, and 1004 were evaluable. Vomiting and nausea occurred in 11.0% and 27.1% of patients, respectively, and 27.9% patients had both vomiting and nausea. In multifactorial analysis, the only statistically significant patient-related risk factors were concomitant chemotherapy and previous experience of vomiting induced by chemotherapy. Moreover, two radiotherapy-related factors were significant risk factors for RIE, the irradiated site (upper abdomen) and field size (>400 cm 2 ). An antiemetic drug was given only to a minority (17%) of patients receiving RT, and the prescriptions were prophylactic in 12.4% and symptomatic in 4.6%. Different compounds and a wide range of doses and schedules were used. Conclusions: These data were similar to those registered in our previous observational trial, and the radiation oncologists' attitude in underestimating RIE and under prescribing antiemetics was confirmed.

  20. Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Hasan Onur Topcu

    2015-03-01

    Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

  1. The Effect of Transdermal Scopolamine for the Prevention of Postoperative Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Maria A. Antor

    2014-04-01

    Full Text Available Postoperative nausea and vomiting is one of the most common and undesirable complaints recorded in as many as 70%-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 hours after surgery. In an effort to find a safer and reliable therapy for postoperative nausea and vomiting, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a nonselective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2-scopolamine (tropic acid ester with scopine; MW = 303.4. Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 hours. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in postoperative nausea and vomiting. Thus, scopolamine is a promising candidate for the management of postoperative nausea and vomiting in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long

  2. Clinical roundtable monograph: New data in emerging treatment options for chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S

    2014-03-01

    Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines.

  3. A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

    Science.gov (United States)

    Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

    2007-09-01

    Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

  4. A prospective, randomized, double blind and placebo-control study comparing the additive effect of oral midazolam and clonidine for postoperative nausea and vomiting prophylaxis in granisetron premedicated patients undergoing laparoscopic cholecystecomy

    Directory of Open Access Journals (Sweden)

    Ghanshyam Yadav

    2013-01-01

    Full Text Available Background: Reduction of postoperative nausea and vomiting (PONV continues to be a major challenge in perioperative care in spite of introduction of newer antiemetics with better efficacy and safety profiles. Therefore, we evaluated the additive effect of oral midazolam and clonidine for PONV prophylaxis in granisetron premedicated patients undergoing laparoscopic cholecystectomy. Materials and Methods: In a prospective, randomized fashion, 120 selected cases were randomized into three groups: I, II or III to receive a tablet of midazolam (15 mg, n = 36, clonidine (150 mcg, n = 40, or glucose as placebo (5 g, n = 44 orally, 1 h before anesthesia. Occurrence of PONV along with need for rescue antiemetic during the first postoperative day was compared between groups as a primary outcome. Results: Episodes of PONV reduced significantly in Group II (15% as compared to group I and III (22.2%, 59% at various time points during the period of observation (P = 0.002. Need for rescue antiemetic was significantly lower in group I (13.88% and II (5% as compared to group III (52.27%, P < 0.001. Conclusion: Oral clonidine is better adjuvant for PONV prophylaxis, as compared to midazolam, in granisetron premedicated patients undergoing laparoscopic cholecystectomy.

  5. Observational Case Series Evaluation of the Granisetron Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of Pregnancy.

    Science.gov (United States)

    Le, Tran N; Adler, Michael T; Ouillette, Holly; Berens, Pamela; Smith, Judith A

    2017-07-01

    Objective  The objective of this study was to observe the efficacy of antiemetic therapy (no emesis/retching episodes and no rescue medication use) when granisetron is administered via a transdermal patch system (TDS) in women who are 6 to 14 weeks pregnant when compared with oral ondansetron by evaluating the frequency of the use of rescue medications for control of nausea/vomiting of pregnancy (NVP). Methods  This was an observational case series study to observe the potential benefits of granisetron TDS compared with oral ondansetron for management of NVP in pregnant patients during the first trimester. Dates of data collection were September 1, 2014, through December 31, 2015. There was no direct contact with patient. The oral ondansetron and granisetron TDS patients were matched by age, 4:1. The proportion of patients who received rescue antiemetics was calculated from those patients who continued to experience NVP. Risk factors for NVP were identified and compared between groups. Descriptive statistics were used to describe study results. Results  Patients were prescribed rescue antiemetics in 0/3 patients in the granisetron TDS group compared with 2/12 patients in the oral ondansetron group. Conclusion  Prospective efficacy studies on the use of granisetron TDS for management of NVP are needed to confirm this clinical observation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Efficacy of aprepitant for prevention of postoperative nausea and vomiting. Systematic review and meta-analysis of randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Berrío Valencia, Marta Inés

    2014-10-01

    Full Text Available Objective: To evaluate the efficacy of aprepitant compared with other antiemetics for the prevention of postoperative nausea and vomiting in adults who underwent general anesthesia. Methods: Systematic review of randomized clinical trials with meta-analysis, that evaluated the efficacy of aprepitant in comparatison with other antiemetics for the prevention of postoperative nausea and vomiting, antiemetic rescue and adverse effects. The search was done in The Cochrane Library, EBSCO, EMBASE, LILACS, OVID, PubMed, SciELO, ScienceDirect, Scopus and Google Scholar. Heterogeneity was defined with the Cochran Q and I2 statistic, the model fixed and random effects were used, the Mantel-Haenszel for relative risk of each outcome and its respective confidence interval 95% were used. Results: There was significant difference in favor of aprepitant for the prevention of vomiting at 24 (RR 0.52; 95% CI: 0.38-0.7 and at 48 hours (RR 0.51; 95% CI: 0.39 to 0.67 but not for nausea at 24 hours (RR 1.16; 95% CI: 0.85-1.6. Conclusions: Aprepitant prevents postoperative vomiting, but not nausea, at 24 and 48 hours.

  7. Prevention of acute chemotherapy-induced nausea and vomiting: the role of palonosetron

    International Nuclear Information System (INIS)

    Bajetta, Emilio; Pusceddu, Sara; Guadalupi, Valentina; Ducceschi, Monika; Celio, Luigi

    2009-01-01

    Prevention of nausea and vomiting is the main goal of antiemetic treatment in cancer patients scheduled to receive chemotherapy. To prevent acute emesis, antiemetics should be administered just before chemotherapy and patients should be protected for up to 24 hours after chemotherapy initiation. The emetogenic potential of chemotherapeutic agents guides clinicians towards the most appropriate antiemetic prophylaxis. Current guidelines recommend the use of 5-HT 3 receptor antagonist (RA) either alone or in combination with dexamethasone and/or a neurokinin-1 RA both in the acute and delayed phases. The second-generation 5-HT 3 RA palonosetron exhibits a longer half-life and a higher binding affinity than older antagonists. Palonosetron has been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients scheduled to receive either moderately (MEC) or highly emetogenic chemotherapy (HEC) and for the prevention of delayed CINV in patients receiving MEC. The present review will discuss the role of palonosetron in the prevention of acute CINV

  8. A comparison of the effects of droperidol and the combination of droperidol and ondansetron on postoperative nausea and vomiting for patients undergoing laparoscopic cholecystectomy.

    LENUS (Irish Health Repository)

    Awad, Imad T

    2012-02-03

    STUDY OBJECTIVES: To compare the prophylactic antiemetic efficacy of the combination of ondansetron and droperidol with that of droperidol alone in patients undergoing elective laparoscopic cholecystectomy. DESIGN: Randomized, double-blind controlled trial. University affiliated teaching hospital after induction of standardized general anesthesia. PATIENTS: 64 ASA physical status I or II patients aged 18 to 80 years, undergoing elective laparoscopic cholecystectomy. INTERVENTION: Following induction of general anesthesia, patients received either droperidol 1.25 mg intravenously (IV; n = 30; Group D) or the combination of droperidol 1.25 mg IV and ondansetron 4 mg IV (n = 34; Group D+O). MEASUREMENTS: Number and severity of nausea episodes, number of emetic episodes, total analgesic consumption, and rescue antiemetic administration were assessed at 1, 3, and 24 hours after admission to the recovery room. Data were analyzed using Fisher\\'s Exact test and unpaired Student\\'s t-test; a p-value <0.05 was considered significant. RESULTS: The proportions of patients who experienced nausea (70% and 53% for D and D+O groups, respectively) and vomiting (30% and 19% for D and D+O groups, respectively) were similar in the two groups. The frequency of moderate and severe nausea (requiring administration of antiemetic) was less in group D + O (7%) compared with group D (19%; p < 0.05). CONCLUSIONS: Patients who received the combination of droperidol and ondansetron experienced less severe nausea compared with patients who received droperidol alone.

  9. [Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

    Science.gov (United States)

    Martín, M; Díaz-Rubio, E

    1989-06-10

    Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

  10. [The Effectiveness of Epidural Droperidol for Prophylaxis of Postoperative Nausea and Vomiting: A Comparative Study of Droperidol and Adrenaline].

    Science.gov (United States)

    Toyonaga, Shinya; Shinozuka, Norihiro; Dobashi, Tamae; Iiyori, Nao; Sudo, Tomoko

    2016-05-01

    Intravenous droperidol has strong evidence for antiemetic efficacy in high risk patients for prevention of postoperative nausea and vomiting (PONV). However it is not clear whether continuous epidural administration of doroperidol prevent PONV. It has been reported that epidural adrenaline decreases PONV; therefore we prospectively compared the effectiveness of epidural droperidol and adrenaline for prophylaxis of PONV. Eighty-six patients were scheduled for abdominal gynecological surgery under general-epidural anesthesia in the study. Patients were randomly assigned to droperidol group or adrenaline group. We investigated the incidences of PONV, the frequency of using the antiemetics. There was no statistical difference between the groups. The incidences of PONV were 27.9% (doropeidol group) and 58.1% (adrenaline group), respectively (P = 0.0046). The frequency of the anti-emetics use were 18.6% and 41.9%, respectively (P = 0.0189). There was one patient who needed cancellation of continuous epidural administration for vomiting in adrenaline group, but no patient in doropeidol group. The results suggest that epidural droperidol effectively decreases PONV in high risk patients. However epidural adrenaline might be ineffective.

  11. Contraction of gut smooth muscle cells assessed by fluorescence imaging

    Directory of Open Access Journals (Sweden)

    Yohei Tokita

    2015-03-01

    Full Text Available Here we discuss the development of a novel cell imaging system for the evaluation of smooth muscle cell (SMC contraction. SMCs were isolated from the circular and longitudinal muscular layers of mouse small intestine by enzymatic digestion. SMCs were stimulated by test agents, thereafter fixed in acrolein. Actin in fixed SMCs was stained with phalloidin and cell length was determined by measuring diameter at the large end of phalloidin-stained strings within the cells. The contractile response was taken as the decrease in the average length of a population of stimulated-SMCs. Various mediators and chemically identified compounds of daikenchuto (DKT, pharmaceutical-grade traditional Japanese prokinetics, were examined. Verification of the integrity of SMC morphology by phalloidin and DAPI staining and semi-automatic measurement of cell length using an imaging analyzer was a reliable method by which to quantify the contractile response. Serotonin, substance P, prostaglandin E2 and histamine induced SMC contraction in concentration-dependent manner. Two components of DKT, hydroxy-α-sanshool and hydroxy-β-sanshool, induced contraction of SMCs. We established a novel cell imaging technique to evaluate SMC contractility. This method may facilitate investigation into SMC activity and its role in gastrointestinal motility, and may assist in the discovery of new prokinetic agents.

  12. Effects of Red Wine Vinegar Beverage on the Colonic Tissue of Rodents: Biochemical, Functional and Pharmacological Analyses.

    Science.gov (United States)

    Enkhsaikhan, Azjargal; Takahara, Akira; Nakamura, Yuji; Goto, Ai; Chiba, Koki; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Naito, Atsuhiko T; Sugiyama, Atsushi

    2018-01-01

    A beverage made of red wine vinegar and grape juice (Yamanashi-no-megumi™) was developed as a supplemental fluid containing polyphenols, which has been clinically shown to enhance the colonic transit. In this study, we assessed the mechanism of its prokinetic action by analyzing the effects on both the colonic phosphodiesterase activity of rats (n=4) and the isolated colonic strip preparation of guinea pigs (n=4). The 7% (v/v) solution of the beverage significantly decreased the phosphodiesterase activity by 9% (n=4). The beverage in concentrations of 0.7, 2.1 and 7% (v/v) relaxed the colonic strips pre-contracted by 1 µmol/L of carbachol in a concentration-related manner with 50, 58 and 79%, each response of which was diminished to 11, 19 and 46%, respectively in the presence of 100 µmol/L of L-nitro-arginine methyl ester. These results obtained by biochemical, functional and pharmacological analyses suggest that the beverage could relax the colon through both cAMP-associated and nitric oxide-dependent pathways, which may partly explain clinically observed prokinetic effect of the beverage.

  13. Combination could be another tool for bowel preparation?

    Science.gov (United States)

    Soh, Jae Seung; Kim, Kyung-Jo

    2016-01-01

    Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol (PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents (e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents (e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents (e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients’ adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies. PMID:26973388

  14. Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.

    Directory of Open Access Journals (Sweden)

    Tamhane M

    1997-01-01

    Full Text Available Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex were divided into four groups as follows--Group 1 (n = 15 normal animals; Group II (n = 6 rats administered metoclopramide (1.35 mg/kg; Group III (n = 8 rats given atropine (0.45 mg/kg. These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8 were administered Terminalia chebula (100 mg/kg/day for 15 days orally. Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5% mixed with phenol red (50 mg/100 ml orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01 and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01. Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01. Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.

  15. In vivo pharmacological activities of methanolic extract of Tabernaemontana recurva Roxb.

    Directory of Open Access Journals (Sweden)

    Robel Chandra Singha

    2017-09-01

    Full Text Available Objective: To evaluate analgesic, hypoglycemic, anxiolytic, and anthelmintic activities with phytochemical screening of methanolic extract of Tabernaemontana recurva (T. recurva whole plants. Methods: The plant parts of T. recurva were collected, dried, powdered and extracted with methanol. Then the extracts were subjected to in vivo analgesic, hypoglycemic, anxiolytic activity in mice model and in vitro anthelmintic activity. Results: The analysis of phytochemical screening confirmed the existence of alkaloid, saponin, tannins, carbohydrate, phytosterols, glycosides and phenol. In analgesic test, a significant level of percentage inhibition of abdominal constriction was observed with concentration of 200 and 400 mg/kg of body weight of extract and this was found better with formalin induced hind paw licking test rather than acetic acid induced writhing test. In hypoglycemic test, it was observed that concentration 200 mg/kg reduced blood sugar level slightly while concentration 400 mg/ kg increased glucose level by 22.95%. A significant level of anxiolytic activity was observed for the study plant extract. The extract revealed potent anthelmintic activity at different concentrations. Conclusions: In light, the methanolic extract of T. recurva exhibited excellent anthelmintic, anxiolytic and analgesic activity. This plant showed moderate hypoglycemic effect at lower concentration but higher concentration increased blood glucose level.

  16. ТЕРАПИЯ ТРЕВОЖНЫХ РАССТРОЙСТВ У ПАЦИЕНТОВ С СЕРДЕЧНО-СОСУДИСТЫМИ ЗАБОЛЕВАНИЯМИ (ОПЫТ ПРИМЕНЕНИЯ АФОБАЗОЛА

    Directory of Open Access Journals (Sweden)

    В. Э. Медведев

    2013-01-01

    Full Text Available According to modern researches data, patients with cardiovascular diseases often suffer from symptoms of anxiety-phobic, panic, somatoform disorders and hypochondria. One of the most common signs of psychopathological disorders in patients with cardiovascular diseases are anxiety symptoms. Development and introduction into clinical practice of new Russian anxiolytic Afobazol had opened new perspectives in the treatment of those patients.

  17. ТЕРАПИЯ ТРЕВОЖНЫХ РАССТРОЙСТВ У ПАЦИЕНТОВ С СЕРДЕЧНО-СОСУДИСТЫМИ ЗАБОЛЕВАНИЯМИ (ОПЫТ ПРИМЕНЕНИЯ АФОБАЗОЛА)

    OpenAIRE

    В. Э. Медведев

    2013-01-01

    According to modern researches data, patients with cardiovascular diseases often suffer from symptoms of anxiety-phobic, panic, somatoform disorders and hypochondria. One of the most common signs of psychopathological disorders in patients with cardiovascular diseases are anxiety symptoms. Development and introduction into clinical practice of new Russian anxiolytic Afobazol had opened new perspectives in the treatment of those patients.

  18. Anxious moments for the protein tyrosine phosphatase PTP1B

    OpenAIRE

    Krishnan, Navasona; Tonks, Nicholas K.

    2015-01-01

    Chronic stress can lead to the development of anxiety and mood disorders. Thus, novel therapies for preventing adverse effects of stress are vitally important. Recently, the protein tyrosine phosphatase PTP1B was identified as a novel regulator of stress-induced anxiety. This opens up exciting opportunities to exploit PTP1B inhibitors as anxiolytics.

  19. ADRENAL HORMONES IN RATS BEFORE AND AFTER STRESS-EXPERIENCE - EFFECTS OF IPSAPIRONE

    NARCIS (Netherlands)

    KORTE, SM; BOUWS, GAH; BOHUS, B

    The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10.

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 268 ... Journal of Pharmaceutical and Allied Sciences. ... of Poloxamer 188 solid dispersions of Indomethacin, Abstract ... Vol 10, No 2 (2013), Prescription pattern of anxiolytic drugs in burn patients: a case study of national ... in two selected secondary health facilities in Bayelsa State of Nigeria, Abstract.

  1. Effects of Lactuca sativa extract on exploratory behavior pattern, locomotor activity and anxiety in mice

    Directory of Open Access Journals (Sweden)

    S.N. Harsha

    2012-05-01

    Full Text Available Objective: To evaluate antianxiety property of Lactuca sativa, an important and commonly used leafy vegetable known for its medicinal properties belongs to Asteraceae family. Methods: Elevated plus maze (EPM, open field test (OFT, rat exposure test, hyponeophagia and marble burying test were performed in mice models to assess the exploratory behaviour and to assess anxiolytic property of hydro-alcohol extract of Lactuca sativa. Diazepam (1 mg/kg body wt. served as the standard anxiolytic agent for all the tests. The dried extract of the plant leaf in doses of 100, 200 and 400 mg/kg body weight was administered orally to mice for duration of 15 or 30 days and evaluated exploratory behaviour, locomotor and anxiolytic activities. Results: Time spent and number of entries into the open arm was measured in EPM followed by total locomotor activity in OFT and latency to enter the food zone in hyponeophagia. Conclusions: The study suggested that hydro-alcohol extract of Lactuca sativa leaves possess potent anxiolytic property.

  2. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California poppy) and its alkaloids

    Science.gov (United States)

    Eschscholzia californica Cham., a native US plant, is traditionally used as a sedative, analgesic and anxiolytic herb. With the rapid rise in the use of herbal supplements together with over the counter (OTC) and prescription drugs, the risk for potential herb-drug interactions is also increasing. M...

  3. A Fatigue Management System for Sustained Military Operations

    Science.gov (United States)

    2008-03-31

    Medications in Sustained Operations – Storm et al. DRAFT anxiolytic, myorelaxant, and anticonvulsant properties, and...sedation in pediatric anesthesia (Scheepers, Montgomery, Kinahan, et al., 2000). Submucosal administration was compared to intravenous administration...Arheart KL, & Mandrell TD (2000). Comparative pharmacokinetics of submucosal vs. intravenous flumazenil (Romazicon) in an animal model. Pediatr

  4. Use of psychotropic medication among inpatients during focused efforts in prevention of coercion and restraint

    DEFF Research Database (Denmark)

    Højlund, Mikkel; Høgh, Lene; Munk-Jørgensen, Povl

    Objective: Department of Psychiatry in Aabenraa participates in a national Danish project supporting efforts to reduce coercion and restraint in psychiatry. Antipsychotic and anxiolytic medicine is widely used among agitated patients, but is also known to contribute to cardio-vascular disease...

  5. Making Sense of Fear Testing - Validating Common Behavioral Tests used in Swine

    Science.gov (United States)

    Tests to assess fear are commonly used in laboratory animals, such as mice and rats, when researchers wish to understand the implications of specific drugs, such as anxiolytics, or specific environments which may be used to house experimental animals. Researchers who study the welfare of livestock ...

  6. Levomepromazine (methotrimeprazine) and the last 48 hours.

    Science.gov (United States)

    O'Neill, J; Fountain, A

    1999-08-01

    Levomepromazine (previously known as methotrimeprazine) has a broad range of beneficial effects in the terminal phase of many illnesses, resulting from its combined antipsychotic, anxiolytic and sedative actions. Levomepromazine can safely be administered in a continuous subcutaneous infusion with most other commonly used drugs in palliative care.

  7. Children's Memories for Painful Cancer Treatment Procedures: Implications for Distress.

    Science.gov (United States)

    Chen, Edith; Zeltzer, Lonnie K.; Craske, Michelle G.; Katz, Ernest R.

    2000-01-01

    Examined memory of 3- to 18-year-olds with leukemia regarding lumbar punctures (LP). Found that children displayed considerable accuracy for event details, with accuracy increasing with age. Use of Versed (anxiolytic medication described as a "memory blocker") was not related to recall. Higher distress predicted greater exaggerations in…

  8. Scorpion sting in the right ear of a young adult: a case report ...

    African Journals Online (AJOL)

    He had made attempts to remove the insect with the cotton bud but all proved abortive. Two drops of 2% plain xylocaine and 5 drops of cerumol were applied on the affected ear. He was managed with analgesics, anxiolytic, antihistamine and ear syringing. The family physician; a frontline doctor and first point of contact for ...

  9. Antidepressant and antioxidant activities of Artemisia absinthium L ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-15

    Dec 15, 2009 ... Mora S, Millıan R, Lungenstrass H, Dııaz-Vıeliz G, Morıan JA, Herrera-. Ruiz M, Tortoriello J (2006). The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats. J. Ethnopharmacol. 106: 76-81. Morteza-Semnani K, Mahmoudi M, Riahi G (2007). Effects of essential.

  10. Author Details

    African Journals Online (AJOL)

    Faborode, Samuel Oluwaseun. Vol 19, No 3 (2016) - RESEARCH ARTICLE The Anxiolytic Properties of Vernonia Amygdalina (Asteraceae) in Laboratory Mice Abstract PDF. ISSN: 1119-5096. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  11. 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 ...

  12. Author Details

    African Journals Online (AJOL)

    Uzondu, ALE. Vol 10, No 2 (2013) - Articles Antimicrobial spectra and activities of antibiotic substances from Streptomyces species against sensitive and resistant microorganisms. Abstract · Vol 10, No 2 (2013) - Articles Prescription pattern of anxiolytic drugs in burn patients: a case study of national orthopaedic hospital, ...

  13. West African Journal of Pharmacology and Drug Research - Vol 19 ...

    African Journals Online (AJOL)

    Anxiolytic and Muscle-Relaxant Activities of Dalbergia saxatilis · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. OK Yemitan, OO Adeyemi, 42-46. http://dx.doi.org/10.4314/wajpdr.v19i1.14732 ...

  14. Author Details

    African Journals Online (AJOL)

    Agboola, IO. Vol 4, No 5 (2010) - Articles Anxiolytic effect of aridanin isolated from Tetrapleura tetraptera in mice. Abstract PDF. ISSN: 1997-342X. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use ...

  15. Download this PDF file

    African Journals Online (AJOL)

    Mr Olusoji

    Symptomatic and improve lung maturity, pethidine/pentazocine supportive care was the modality of management. injection PRN because of severe pain, sitz bath with Judicious analgesics and anxiolytics wererequired chlohexidine solution and Chymoral, an antitypsin because of pain and anxiety. Mechanical drainage.

  16. 2018-03-29T06:45:33Z https://www.ajol.info/index.php/all/oai oai:ojs ...

    African Journals Online (AJOL)

    The possible effect of H musciformis on dopamine and other brain biogenic amines indicate that H musciformis probably have psychotropic and anxiolytic profile. The increased level of dopamine could also be beneficial keeping in view the etiology of Parkinsonism. In present study the level of serotonin was found to be ...

  17. Phytopharmacology and medicinal properties of Salix aegyptiaca L ...

    African Journals Online (AJOL)

    S. aegyptiaca has recently been shown to have antioxidant, anxiolytic activity and hypocholestrolemic effect. High amounts of phenols and flavonoids such as gallic acid, caffeic acid, myricetin, catechin, quercetin as well as salicin, are reported from the leaves of this plant. 1,4-dimethoxybenzene, phenylethyl alcohol, ...

  18. Author Details

    African Journals Online (AJOL)

    Neteydji, Sidiki. Vol 13, No 4 (2016) - Articles Anxiolytic - like properties of Hallea ciliata in mice. Abstract PDF. ISSN: 0189-6016. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL ...

  19. Author Details

    African Journals Online (AJOL)

    Okafor, JO. Vol 10, No 2 (2013) - Articles Prescription pattern of anxiolytic drugs in burn patients: a case study of national orthopaedic hospital, Enugu, Nigeria Abstract. ISSN: 1596-8499. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

  20. FLAVONOIDS FROM THE ROOTS OF DIOCLEA REFLEXA (HOOK F.)

    African Journals Online (AJOL)

    B. S. Chandravanshi

    anticonvulsant, anxiolytic [2], antioxidant [3], antiarrhythmogenic [4], immunodulatory [5], analgesic and central antinociceptive effects [6], which have been identified with Dioclea plants. Dioclea reflexa (Hook F.) is a woody climber, which produces flowers and pods on long rope- like stems that hang from the forest canopy.