Potentiators of responses to activation of gamma-aminobutyric acid (GABAA) receptors

Abstract

Quantitative aspects of the potentiation of GABA and muscimol by benzodiazepines and barbiturates are reviewed, taking account of both electrophysiological and receptor binding data. It has been a consistent finding that barbiturates cause a greater maximal potentiation than do benzodiazepines. The steroid anaesthetic alphaxalone and some naturally occurring steroids were compared as potentiators of electrophysiological responses to muscimol. From the relative potencies, important structural features of the steroid molecule for this effect have been identified. The possibility of the barbiturates and the steroids having a common mode of action as potentiators of GABA and muscimol is discussed, together with the idea that this action may involve perturbation of membrane lipids rather than a barbiturate/steroid receptor site. The GABA-potentiating effect of ethanol may also be barbiturate-like but potentiations by chlormethiazole and ketamine appear to involve different mechanisms. It is predicted that any endogenous potentiators of GABA would be unlikely to have more than a modest effect.