Convulsant component of a depressant benzodiazepine.
The convulsant influence of high doses of diazepam, in the presence of the benzodiazepine receptor antagonist Ro 15-1788, was studied in rats. Animals were implanted with permanent cortical screw electrodes for EEG recording. EEG spiking and accompanying clonic activity was observed in rats receiving greater than or equal to 200 mg/kg diazepam, followed 10 minutes later by Ro 15-1788 (20 mg/kg). Pentylenetetrazole and picrotoxin seizure thresholds, measured during constant rate iv infusion, were significantly lowered by pretreatment with diazepam (250 mg/kg) and Ro 15-1788 (20 mg/kg) administered 30 and 20 minutes, respectively, before seizure threshold measurement. It is proposed that this convulsive activity of diazepam is mediated through the picrotoxinin receptor.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced*
D001570:Benzodiazepinones; D003975:Diazepam; D005442:Flumazenil; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011963:Receptors, GABA-A; C037480:picrotoxinin receptor