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Selective Antagonism of GABAA Receptor Subtypes: An In Vivo Approach to Exploring the Therapeutic and Side Effects of Benzodiazepine–Type Drugs

Published online by Cambridge University Press:  07 November 2014

James K. Rowlett ,
James M. Cook ,
Angela N. Duke  and
Donna M. Platt
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Abstract

Benzodiazepines (BZs) are clinically used as anxiolytic, hypnotic, anticonvulsant, and antispasmodic drugs. Research using transgenic mouse models has suggested that the effects of BZs involve multiple subtypes of the γ-aminobutyric acid type A (GABAA) receptor, identified by specific α subunits (α1, α2, α3, α5). This review discusses the experimental uses of β-carboline-3-carboxylate-t-butyl ester (βCCT), a drug that binds preferentially to the GABAA α1 subtype but exerts no action (ie, is a pharmacologic antagonist at the GABAA α1 subtype receptor). βCCT blocks the anxiolytic-like effects of BZs, although studies in primates suggests this antagonism may reflect multiple receptor populations. βCCT antagonized the ataxic but not muscle relaxant effects of BZs, a finding that implicates the GABAA α1 subtype receptor in ataxia but not muscle relaxation. The potential clinical utility of βCCT is discussed, both in terms of treatment (ie, hepatic encephalopathy) and as a diagnostic imaging agent. Altogether, these results indicate that subtype-selective antagonists represent a useful approach to studying receptor mechanisms underlying the behavioral effects of BZ-type drugs.

Type
Review Article
Information
CNS Spectrums , Volume 10 , Issue 1 , January 2005 , pp. 40 - 48
Copyright
Copyright © Cambridge University Press 2005

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