Pro- and anti-convulsant drug effects in combination with the convulsant benzodiazepine Ro 5-4864.
The effects of several compounds believed to act at the GABA-benzodiazepine receptor complex and which have anticonvulsant or proconvulsant properties when administered in combination with picrotoxin and pentetrazol (leptazol, pentylenetetrazole) were investigated in combination with the convulsant benzodiazepine Ro 5-4864. Tracazolate (25-100 mg kg-1) failed to affect convulsions induced by Ro 5-4864; however, they were prevented by treatment with CL 218,872 (20 mg kg-1). Compounds having proconvulsant activity in combination with a subthreshold dose of Ro 5-4864 were: CL 218,872 (5 mg kg-1), and CGS 8216 (20 mg kg-1) and FG 7142 (40 mg kg-1), two compounds characterized as 'inverse agonists' at benzodiazepine receptors. The phenylquinolines PK 8165 and PK 9084, originally believed to have anxiolytic properties, had no significant effect in combination with Ro 5-4864 (25-100 mg kg-1). The convulsant profile of Ro 5-4864 is compared with that of picrotoxin and pentetrazol.
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D002243:Carbolines; D003292:Convulsants; D011720:Pyrazoles; D011724:Pyridazines; D011804:Quinolines; C028513:4'-chlorodiazepam; C035874:FG 7142; C021604:CL 218872; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; C030078:pipequaline; C034317:tracazolate