Antagonism of the intoxicating effects of ethanol by the potent benzodiazepine receptor ligand Ro 19-4603

The effects of the imidazothienodiazepinone Ro 19-4603 were investigated in mice. Ro 19-4603 (0.03–0.3 mg/kg) caused a dose-related reduction in seizure threshold to i.v. bicuculline. Doses of 0.1–3 mg/kg induced seizures in some but not all mice, consistent with its suggested action as a partial benzodiazepine receptor inverse agonist. Ro 19-4603 (0.01–0.3 mg/kg) attenuated the intoxicating effects of ethanol (2.4 g/kg) and was as effective as Ro 15-4513 in this respect.