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.
D000818:Animals; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003292:Convulsants; D003975:Diazepam / Q000494:pharmacology; D004357:Drug Synergism; D005442:Flumazenil; D008297:Male; D051379:Mice; D010852:Picrotoxin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control
D001570:Benzodiazepinones; D003292:Convulsants; D003975:Diazepam; D005442:Flumazenil; D010852:Picrotoxin; D011720:Pyrazoles; D011804:Quinolines; C022193:Ro 5-3663; C030079:PK 9084; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; C030078:pipequaline