The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Danka Peričić - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of short- and long-term zolpidem treatment on recombinant α1β2γ2s subtype of GABA_A receptors in vitro
Acta Pharmacologica Sinica, 2012Co-Authors: Josipa Vlainić, Maja Jazvinšćak Jembrek, Toni Vlainić, Dubravka Švob Štrac, Danka PeričićAbstract:Aim: Zolpidem is a non-benzodiazepine agonist at benzodiazepine binding site in GABA_A receptors, which is increasingly prescribed. Recent studies suggest that prolonged zolpidem treatment induces tolerance. The aim of this study was to explore the adaptive changes in GABA_A receptors following short and long-term exposure to zolpidem in vitro . Methods: Human embryonic kidney (HEK) 293 cells stably expressing recombinant α1β2γ2s GABA_A receptors were exposed to zolpidem (1 and 10 μmol/L) for short-term (2 h daily for 1, 2, or 3 consecutive days) or long-term (continuously for 48 h). Radioligand binding studies were used to determine the parameters of [^3H]Flunitrazepam binding sites. Results: A single (2 h) or repeated (2 h daily for 2 or 3 d) short-term exposure to zolpidem affected neither the maximum number of [^3H]Flunitrazepam binding sites nor the affinity. In both control and short-term zolpidem treated groups, addition of GABA (1 nmol/L–1 mmol/L) enhanced [^3H]Flunitrazepam binding in a concentration-dependent manner. The maximum enhancement of [^3H]Flunitrazepam binding in short-term zolpidem treated group was not significantly different from that in the control group. In contrast, long-term exposure to zolpidem resulted in significantly increase in the maximum number of [^3H]Flunitrazepam binding sites without changing the affinity. Furthermore, long-term exposure to zolpidem significantly decreased the ability of GABA to stimulate [^3H]Flunitrazepam binding. Conclusion: The results suggest that continuous, but not intermittent and short-term, zolpidem-exposure is able to induce adaptive changes in GABA_A receptors that could be related to the development of tolerance and dependence.
Pierre Denise - One of the best experts on this subject based on the ideXlab platform.
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residual effects of zolpidem 10 mg and zopiclone 7 5 mg versus Flunitrazepam 1 mg and placebo on driving performance and ocular saccades
Psychopharmacology, 1999Co-Authors: Marielaure Bocca, Le F Doze, Olivier Etard, M Pottier, J Lhoste, Pierre DeniseAbstract:Rationale: Studies report contradictory results concerning the residual effects of zolpidem and zopiclone. Moreover, residual effects of these compounds on healthy subjects have not yet been simultaneously assessed. Objective: The present study with healthy subjects investigated the residual effects of zolpidem 10 mg and zopiclone 7.5 mg on driving performance and on ocular saccade and compared them to those under Flunitrazepam 1 mg and placebo. Methods: The study involved 16 subjects divided into two groups, a 9:00 a.m. group and a 11:00 a.m. group, in a balanced, double-blind, cross-over design. Results: In the 9:00 a.m. group, zolpidem had no residual effects while zopiclone and Flunitrazepam both impaired driving performance (P < 0.001 for both) and increased saccadic latency (P < 0.005; P = 0.052, respectively). Zopiclone impaired driving performance 5 times less than did Flunitrazepam. In the 11:00 a.m. group, zolpidem and zopiclone had no residual effects, while Flunitrazepam increased saccadic latency (P = 0.065) but did not impair driving performance. Conclusions: Zopiclone and Flunitrazepam had residual effects in the first part of the morning, whereas zolpidem had no residual effects. The hierarchical character of the effects of the molecules differed according to the test administered. This is probably linked more to drug-induced specific alterations than to different sensitivities of the tests.
Josipa Vlainić - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of short- and long-term zolpidem treatment on recombinant α1β2γ2s subtype of GABA_A receptors in vitro
Acta Pharmacologica Sinica, 2012Co-Authors: Josipa Vlainić, Maja Jazvinšćak Jembrek, Toni Vlainić, Dubravka Švob Štrac, Danka PeričićAbstract:Aim: Zolpidem is a non-benzodiazepine agonist at benzodiazepine binding site in GABA_A receptors, which is increasingly prescribed. Recent studies suggest that prolonged zolpidem treatment induces tolerance. The aim of this study was to explore the adaptive changes in GABA_A receptors following short and long-term exposure to zolpidem in vitro . Methods: Human embryonic kidney (HEK) 293 cells stably expressing recombinant α1β2γ2s GABA_A receptors were exposed to zolpidem (1 and 10 μmol/L) for short-term (2 h daily for 1, 2, or 3 consecutive days) or long-term (continuously for 48 h). Radioligand binding studies were used to determine the parameters of [^3H]Flunitrazepam binding sites. Results: A single (2 h) or repeated (2 h daily for 2 or 3 d) short-term exposure to zolpidem affected neither the maximum number of [^3H]Flunitrazepam binding sites nor the affinity. In both control and short-term zolpidem treated groups, addition of GABA (1 nmol/L–1 mmol/L) enhanced [^3H]Flunitrazepam binding in a concentration-dependent manner. The maximum enhancement of [^3H]Flunitrazepam binding in short-term zolpidem treated group was not significantly different from that in the control group. In contrast, long-term exposure to zolpidem resulted in significantly increase in the maximum number of [^3H]Flunitrazepam binding sites without changing the affinity. Furthermore, long-term exposure to zolpidem significantly decreased the ability of GABA to stimulate [^3H]Flunitrazepam binding. Conclusion: The results suggest that continuous, but not intermittent and short-term, zolpidem-exposure is able to induce adaptive changes in GABA_A receptors that could be related to the development of tolerance and dependence.
James H Woods - One of the best experts on this subject based on the ideXlab platform.
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behavioral effects of Flunitrazepam reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital dependent rats
Drug and Alcohol Dependence, 2001Co-Authors: Lisa R Gerak, Gail Winger, William L Woolverton, Michael A Nader, G A Patrick, Louis S Harris, James H WoodsAbstract:Abstract Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2–4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of Flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, Flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3–6/group), signs of withdrawal were not evident when Flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or Flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of Flunitrazepam is comparable to that of other benzodiazepines.
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abuse liability of Flunitrazepam
Journal of Clinical Psychopharmacology, 1997Co-Authors: James H Woods, Gail WingerAbstract:Flunitrazepam is among the most frequently prescribed hypnotics in many countries.Although it was never marketed in the United States, Flunitrazepam, in recent years, has been smuggled into the country, and reports of abuse-including alleged use of the drug to facilitate "date rape"-have attracted a great deal of scrutiny. It has been suggested that Flunitrazepam may have greater liability for abuse than other benzodiazepines; such suggestions are supported by surveys of opioid abusers, many of whom report a distinct preference for Flunitrazepam over other benzodiazepines. Experimental studies of animals and normal human subjects indicate that, although Flunitrazepam has high efficacy and is very potent, it is pharmacologically similar to most other benzodiazepines. Although the studies are limited in number and scope, the data show no apparent differences between Flunitrazepam and other benzodiazepines in ability to produce drug-taking or drug-seeking behavior, in capacity to produce physiologic dependence, nor in the characteristics of withdrawal after administration of an antagonist or discontinuation of treatment. Similar to other benzodiazepines, Flunitrazepam produces dose-dependent effects on psychomotor performance and recall. Flunitrazepam does not seem to be involved in medical emergencies more often than other benzodiazepines, and there is no indication that Flunitrazepam is more toxic than other benzodiazepines when taken in overdose by drug abusers or other individuals. Survey research among typical patient populations suggests that Flunitrazepam is characteristic of benzodiazepines in that it is used appropriately and conservatively, with low liability for abuse. Thus the reported preference for Flunitrazepam among opioid abusers seems to be the only way in which Flunitrazepam is distinguished from other benzodiazepines; it is unclear what characteristics of the drug may be responsible for this reported preference. The evidence considered in this review indicates that abuse of Flunitrazepam in this special population is not associated with any distinctive threats to the health of the general public. (J Clin Psychopharmacol 1997;17[suppl 2]:1S-57S)
Marielaure Bocca - One of the best experts on this subject based on the ideXlab platform.
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residual effects of zolpidem 10 mg and zopiclone 7 5 mg versus Flunitrazepam 1 mg and placebo on driving performance and ocular saccades
Psychopharmacology, 1999Co-Authors: Marielaure Bocca, Le F Doze, Olivier Etard, M Pottier, J Lhoste, Pierre DeniseAbstract:Rationale: Studies report contradictory results concerning the residual effects of zolpidem and zopiclone. Moreover, residual effects of these compounds on healthy subjects have not yet been simultaneously assessed. Objective: The present study with healthy subjects investigated the residual effects of zolpidem 10 mg and zopiclone 7.5 mg on driving performance and on ocular saccade and compared them to those under Flunitrazepam 1 mg and placebo. Methods: The study involved 16 subjects divided into two groups, a 9:00 a.m. group and a 11:00 a.m. group, in a balanced, double-blind, cross-over design. Results: In the 9:00 a.m. group, zolpidem had no residual effects while zopiclone and Flunitrazepam both impaired driving performance (P < 0.001 for both) and increased saccadic latency (P < 0.005; P = 0.052, respectively). Zopiclone impaired driving performance 5 times less than did Flunitrazepam. In the 11:00 a.m. group, zolpidem and zopiclone had no residual effects, while Flunitrazepam increased saccadic latency (P = 0.065) but did not impair driving performance. Conclusions: Zopiclone and Flunitrazepam had residual effects in the first part of the morning, whereas zolpidem had no residual effects. The hierarchical character of the effects of the molecules differed according to the test administered. This is probably linked more to drug-induced specific alterations than to different sensitivities of the tests.