RO 15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal

RO 15-4513, an imidazodiazepine that has been reported to reverse some of the behavioral effects of ethanol, was given to DBA/2 mice. Although no animals treated with a 6 mg/kg dose of this drug had seizures, 20% of animals given 20 mg/kg of this drug had tonic seizures. Ethanol withdrawal was induced in DBA/2 mice treated with 4-methyl pyrazole using an inhalation paradigm. Mice were more likely to have a seizure during ethanol withdrawal if treated with RO 15-4513 (6 mg/kg) than if they received the vehicle. These data suggest administering RO 15-4513 as an alcohol antagonist to alcoholic subjects may increase the incidence of seizures.