The effects of propofol, pentobarbital, alphaxalone, etomidate and diazepam on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to membrane preparations from rat cerebral cortex were studied in the absence of gamma-aminobutyric acid (GABA). Addition of low concentrations (3-10 microM) of propofol to washed membrane preparations (devoid of GABA) markedly enhanced [35S]TBPS binding (maximal enhancement, 85%), whereas higher concentrations (50-100 microM) inhibited this parameter. Diazepam also enhanced [35S]TBPS binding in this preparation (maximal enhancement, 38%). In contrast, pentobarbital, alphaxalone and etomidate decreased [35S]TBPS binding in a concentration-dependent manner. The propofol-induced increase in [35S]TBPS binding in washed membranes was completely reversed by the addition of GABA at a concentration (0.3 microM) that alone did not modify [35S]TBPS binding (78% increase with 10 microM propofol alone, 33% decrease in the additional presence of GABA). The ability of GABA to reverse the effect of propofol on [35S]TBPS binding in washed membranes was shared by pentobarbital (200 microM) and alphaxalone (3 microM); etomidate (20 microM) only partially antagonized the effect of propofol. Diazepam at a concentration (30 microM) that alone had no effect on [35S]TBPS binding failed to modify the propofol-induced increase in [35S]TBPS binding, whereas at a concentration (3 microM) that alone increased [35S]TBPS binding the effect of diazepam was additive with that of propofol. The addition of bicuculline to washed membranes failed to abolish the increase in [35S]TBPS binding induced by propofol or diazepam, but completely antagonized the effects of pentobarbital, alphaxalone and etomidate.(ABSTRACT TRUNCATED AT 250 WORDS)