Interactions of two phenylquinolines with picrotoxin and benzodiazepines in vivo and in vitro

Abstract

PK 8165 and PK 9084 are phenylquinolines with high affinity for the benzodiazepine binding site. Both phenylquinolines were proconsulvant in combination with subconvulsant doses of picrotoxin and pentylenetetrazole in mice. Both chlordiazepoxide (10 mg/kg) and the imidazodiazepine, RO 15-1788 (10 mg/kg) prevented these tonic-clonic convulsions. In vitro studies of rat cuneate nucleus indicated that the proconvulsant actions of PK 8165 and PK 9084 could be explained by their direct, albeit slightly different, interactions with the GABA-receptor complex. PK 8165 (100 μM) alone had no effect on responses to the GABA analogue muscimol, but enhanced the potency of picrotoxin as an antagonist of muscimol and reduced the potency of flurazepam as a potentiator of muscimol. PK 9084 (100 μM) alone caused a small antagonism of muscimol, but did not affect the potency of picrotoxin; flurazepam reversed the effect of PK 9084.