Effects of acute and chronic treatment on the pro-and anti-convulsant actions of CL 218, 872, PK 8165 and PK 9084, putative ligands for the benzodiazepine receptor

CL 218,872 is a triazolopyridazine that acts at the benzodiazepine binding site. At low doses (0.5-7.5 mg kg-1) it is proconvulsant when combined with subconvulsant doses of picrotoxin but not when combined with pentetrazol (leptazol, pentylenetetrazol). At high doses (20-60 mg kg-1) CL 218,872 counteracted seizures caused by pentetrazol but not those caused by picrotoxin. There was tolerance to the proconvulsant effects after five days of treatment and to the anticonvulsant effects after 15-20 days. Two phenylquinolines, PK 8165 and PK 9084, that also act at the GABA-benzodiazepine receptor complex have proconvulsant actions in combination with picrotoxin. Significant tolerance to these effects had not developed even after 20 days of treatment. It is concluded that three different sites on the GABA-benzodiazepine complex mediate the pro- and anti-convulsant actions of CL 218,872 and the proconvulsant actions of PK 8165 and PK 9084.