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.