Absence of intrinsic antagonist actions of benzodiazepine antagonists on an exploratory model of anxiety in the mouse

J. N. Crawley; P. Skolnic; S. M. Paul

doi:10.1016/0028-3908(84)90026-1

Absence of intrinsic antagonist actions of benzodiazepine antagonists on an exploratory model of anxiety in the mouse

J. N. Crawley, P. Skolnic, S. M. Paul

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

Recent reports suggest that antagonists of benzodiazepine receptors have intrinsic anxiogenic and convulsant properties. An exploratory model in the mouse, specific for anxiolytics, was employed to test further, the hypothesis that antagonists have intrinsic actions pharmacologically opposite to those of the benzodiazepines. The drugs Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidiazo-[1,5-a][1,4]benzodiazepine-3-carboxylate), CGS-8216 (2-phenylpyrazolo[4,3-c]quinolin-3[5H]one),β-CCM (3-carbomethoxy-β-carboline) and FG-7142 (N¹-methyl-β-carbo]ine-3-carboxamide) all effectively blocked the anxiolytic actions of diazepam. None of these antagonists demonstrated intrinsic or anxiogenic or anxiolytic activity in this model system. These findings suggest that both the species and paradigm employed will determine the pharmacological profile of drugs which act at the GABA-benzodiazepine receptor complex.

Original language	English
Pages (from-to)	531-537
Number of pages	7
Journal	Neuropharmacology
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/0028-3908(84)90026-1
State	Published - May 1984

Keywords

antagonists
anxiety
benzodiazepine receptor
β-carbolines

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10.1016/0028-3908(84)90026-1

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abstract = "Recent reports suggest that antagonists of benzodiazepine receptors have intrinsic anxiogenic and convulsant properties. An exploratory model in the mouse, specific for anxiolytics, was employed to test further, the hypothesis that antagonists have intrinsic actions pharmacologically opposite to those of the benzodiazepines. The drugs Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidiazo-[1,5-a][1,4]benzodiazepine-3-carboxylate), CGS-8216 (2-phenylpyrazolo[4,3-c]quinolin-3[5H]one),β-CCM (3-carbomethoxy-β-carboline) and FG-7142 (N1-methyl-β-carbo]ine-3-carboxamide) all effectively blocked the anxiolytic actions of diazepam. None of these antagonists demonstrated intrinsic or anxiogenic or anxiolytic activity in this model system. These findings suggest that both the species and paradigm employed will determine the pharmacological profile of drugs which act at the GABA-benzodiazepine receptor complex.",

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AB - Recent reports suggest that antagonists of benzodiazepine receptors have intrinsic anxiogenic and convulsant properties. An exploratory model in the mouse, specific for anxiolytics, was employed to test further, the hypothesis that antagonists have intrinsic actions pharmacologically opposite to those of the benzodiazepines. The drugs Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidiazo-[1,5-a][1,4]benzodiazepine-3-carboxylate), CGS-8216 (2-phenylpyrazolo[4,3-c]quinolin-3[5H]one),β-CCM (3-carbomethoxy-β-carboline) and FG-7142 (N1-methyl-β-carbo]ine-3-carboxamide) all effectively blocked the anxiolytic actions of diazepam. None of these antagonists demonstrated intrinsic or anxiogenic or anxiolytic activity in this model system. These findings suggest that both the species and paradigm employed will determine the pharmacological profile of drugs which act at the GABA-benzodiazepine receptor complex.

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Absence of intrinsic antagonist actions of benzodiazepine antagonists on an exploratory model of anxiety in the mouse

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Keywords

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