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Benzodiazepines on trial: a research strategy for their rehabilitation.

Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, tolerance, dependence, and the potential for drug abuse plague the clinical use of anxiolytic benzodiazepines. Benzodiazepine and non-benzodiazepine ligands that are in current clinical use act as full allosteric modulators of GABA-gated Cl- channels, and on chronic administration trigger compensatory changes in the subunit expression of GABAA receptors. In these putative abnormal receptors, full allosteric modulators have low intrinsic activity and potency, and tolerance and dependence ensue. In this review, Erminio Costa and Alessandro Guidotti discuss the development of partial allosteric modulators, such as imidazenil, which have high potency and low intrinsic activity at GABA-gated Cl- channels. Since in animals tolerant to full allosteric modulators imidazenil also fails to show cross-tolerance, it is an example of a new type of anxiolytic and anticonvulsant drug acting at GABAA receptors via benzodiazepine recognition sites.[1]

References

  1. Benzodiazepines on trial: a research strategy for their rehabilitation. Costa, E., Guidotti, A. Trends Pharmacol. Sci. (1996) [Pubmed]
 
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