Selective antagonism of GABAA receptor subtypes: an in vivo approach to exploring the therapeutic and side effects of benzodiazepine-type drugs

CNS Spectr. 2005 Jan;10(1):40-8. doi: 10.1017/s1092852900009895.


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 gamma-aminobutyric acid type A (GABAA) receptor, identified by specific a subunits (alpha1, alpha2, alpha3, alpha5). This review discusses the experimental uses of b-carboline-3-carboxylate-t-butyl ester (betaCCT), a drug that binds preferentially to the GABAA alpha1 subtype but exerts no action (ie, is a pharmacologic antagonist at the GABAA alpha1 subtype receptor). betaCCT blocks the anxiolytic-like effects of BZs, although studies in primates suggests this antagonism may reflect multiple receptor populations. betaCCT antagonized the ataxic but not muscle relaxant effects of BZs, a finding that implicates the GABAA alpha1 subtype receptor in ataxia but not muscle relaxation. The potential clinical utility of betaCCT 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / therapeutic use
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use
  • Anxiety Disorders / drug therapy
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Binding, Competitive / drug effects*
  • GABA Modulators / adverse effects*
  • GABA Modulators / therapeutic use
  • GABA-A Receptor Antagonists*
  • Humans
  • Receptors, GABA-A / classification*
  • Sleep Wake Disorders / drug therapy


  • Anti-Anxiety Agents
  • Anticonvulsants
  • GABA Modulators
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Benzodiazepines