Modification of seizures elicited by the benzodiazepine Ro 5-3663--a comparison with picrotoxin

Ro 5-3663 is a convulsant 1,4-benzodiazepine that does not act at the benzodiazepine, but at the picrotoxin, site. To characterize the behavioural actions of Ro 5-3663, a comparison was made between its effects and those of picrotoxin, when combined with several compounds that act at the GABA-benzodiazepine receptor complex. The quinolines, PK 8165, PK 9084 and CGS 8216 caused myoclonic jerks when combined with subconvulsant doses of Ro 5-3663 or picrotoxin; in combination with picrotoxin they also caused full tonic-clonic convulsions. Ro 15-1788 (1, 10 mg kg-1) caused myoclonic jerks when it was given 10 min before, or at the same time as, subconvulsant doses of either compound. Diazepam (2, 4 mg kg-1) was anticonvulsant against both compounds. However, Ro 15-1788 (10, 20 mg kg-1, 20 min before), PK 8165 (80 mg kg-1) and PK 9084 (60 mg kg-1) were effective only against the convulsions induced by Ro 5-3663. It is not possible to determine whether these differences between Ro 5-3663 and picrotoxin are quantitative or qualitative.