Biphasic effects of Ro 15-1788 on spontaneous petit mal-like seizures in rats.
The effects of various doses of the potent and specific benzodiazepine antagonist Ro 15-1788 were investigated in rats with spontaneous non convulsive, petit mal-like seizures. In preliminary experiments, Ro 15-1788, 2 mg/kg i.p., completely but transiently antagonized the antiepileptic action of diazepam, 2 mg/kg i.p. Ro 15-1788, 2 mg/kg, given alone, exhibited no intrinsic activity. At 10-80 mg/kg, it acted as an antiepileptic; this dose-dependent suppressant effect developed slowly over 20-40 min after injection and was never total even at 80 mg/kg. At the highest dose, Ro 15-1788 also had a transient epileptogenic effect immediately following the injection. These results confirm that Ro 15-1788 is not a pure benzodiazepine antagonist but also has partial 'agonist' and 'inverse agonist' properties.
D000818:Animals; D000927:Anticonvulsants; D001570:Benzodiazepinones / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000503:physiopathology*; D005442:Flumazenil; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D001570:Benzodiazepinones; D003292:Convulsants; D005442:Flumazenil; D003975:Diazepam