Convulsant effect of Ro 5-4864, a peripheral type benzodiazepine, on the baboon (Papio papio).
The effects of Ro 5-4864, a 1,4-benzodiazepine with a high affinity for the peripheral-type benzodiazepine (Bz) binding site, were investigated in the baboon (Papio papio), which is genetically predisposed to epilepsy. A proconvulsant effect of low doses (1-3 mg/kg, i.v.) of Ro 5-4864 was observed by studying its effect on the photic responses induced by intermittent light stimulation in non-photosensitive baboons. Higher doses of Ro 5-4864 (10 mg/kg, i.v.) were overtly convulsant. The Bzs clonazepam and diazepam blocked these convulsant actions of Ro 5-4864 whereas neither Ro 15-1788, an antagonist of central Bz binding sites, nor PK 11 195, an antagonist of peripheral Bz binding sites, had any effect. It thus appeared that the convulsant effect of Ro 5-4864 was not mediated by Bz binding sites of either the central or the peripheral type. It is possible that Ro 5-4864 exerts its convulsant action at the picrotoxin site of the central Bz receptor - gamma-aminobutyric acid receptor-chloride ionophore complex.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil; D007546:Isoquinolines / Q000494:pharmacology; D010215:Papio / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*
D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D005442:Flumazenil; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195