Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance
- 29 February 2000
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 97 (5) , 2314-2319
- https://doi.org/10.1073/pnas.97.5.2314
Abstract
The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl− current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition.Keywords
This publication has 28 references indexed in Scilit:
- FROM GABAA RECEPTOR DIVERSITY EMERGES A UNIFIED VISION OF GABAergic INHIBITIONAnnual Review of Pharmacology and Toxicology, 1998
- Benzodiazepines on trial: a research strategy for their rehabilitationTrends in Pharmacological Sciences, 1996
- Reversible Modification of GABA A Receptor Subunit mRNA Expression During Tolerance to Diazepam-induced Cognition DysfunctionNeuropharmacology, 1996
- Imidazenil: A Potent Benzodiazepine Partial Positive Modulator of GABAergic Transmission Virtually Devoid of Tolerance LiabilityCNS Drug Reviews, 1995
- Comparison of the effects of full and partial allosteric modulators of GABAA receptors on complex behavioral processes in monkeysBehavioural Pharmacology, 1995
- Chronic administration of an anticonvulsant dose of imidazenil fails to induce tolerance of GABAA receptor function in miceEuropean Journal of Pharmacology, 1994
- Triazolam is more efficacious than diazepam in a broad spectrum of recombinant GABAA receptorsEuropean Journal of Pharmacology: Molecular Pharmacology, 1993
- Novel anxiolytics that act as partial agonists at benzodiazepine receptorsTrends in Pharmacological Sciences, 1990
- Human behavioral pharmacology of benzodiazepines: Effects on repeated acquisition and performance of response chainsDrug Development Research, 1990
- Differential effects of phencyclidine and MDA on complex operant behavior in monkeysPharmacology Biochemistry and Behavior, 1984