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.
Lister
R G
RG
Laboratory of Clinical Studies, NIAAA, Bethesda, MD 20892.
Durcan
M J
MJ
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced
D001381:Azepines; D003292:Convulsants; D011963:Receptors, GABA-A; D000431:Ethanol; C056530:Ro 19-4603