Barbiturates with pharmacological profiles similar to that of the benzodiazepines enhance [3H]diazepam binding to rat brain membranes. Diazepam binding was increased by depressant, but not by convulsant, barbiturates. (±)-Pentobarbital enhancement of diazepam binding was saturable. Besides having a direct effect, depressant barbiturates also potentiated muscimol enhancement of diazepam binding. The barbiturate-induced increase of diazepam binding was stereospecific and was blocked by γ-aminobutyric and (GABA) synaptic antagonists [(+)-bicuculline, picrotoxinin, and t-butyl bicyclophosphate esters] and by RO5-3663, the convulsant benzodiazepine. The ability of these antagonists to block barbiturate enhancement suggests that barbiturates may increase diazepam binding by acting on the benzodiazepine-GABA-receptor-ionophore complex.
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