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.
Lister
R G
RG
Laboratory of Clinical Studies, NIAAA, Bethesda, MD 20892.
Karanian
J W
JW
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012640:Seizures / Q000139:chemically induced*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D001386:Azides; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513