Failure of the partial inverse benzodiazepine agonist Ro15-4513 to block the lethal effects of ethanol in rats

The partial inverse benzodiazepine agonist Ro15-4513 has been found to antagonize some of the behavioral and physiological effects of low to moderate doses of ethanol. In the present study, pretreating rats with Ro15-4513 (1, 3, 10, and 30 mg/kg) at doses equal to or greater than those used in prior investigations failed to block the lethal effects of intraperitoneal injections of ethanol at a dose of 5.4 g/kg. These results suggest that the lethal actions of ethanol may involve a mechanism that is not blocked by Ro15-4513, which is known to selectively antagonize ethanol-stimulated chloride uptake via the GABA-coupled chloride ion channel.