Interactions of Pyrethroid Insecticides with GABAA and Peripheral-Type Benzodiazepine Receptors

The acute administration of 1RaS,cis cypermethrin, deltamethrin, fenvalerate and permethrin produced a dose-dependent lowering of the concentration of pentylenetetrazol required to elicit a seizure in rats. The proconvulsant action of cypermethrin displayed stereospecificity in that the 1RaS,cis isomer was the most potent compound tested, while the non-insecticidal isomer, 1SaR,cis cypermethrin, was devoid of proconvulsant activity. Pretreatment of rats with PK 11195, an antagonist of the peripheral-type benzodiazepine binding site, elicited a complete reversal of the proconvulsant actions of both deltamethrin and permethrin. In contrast, pretreatment with phenytoin did not alter the pyrethroid-induced proconvulsant activity. These results suggest that the effects of pyrethroids on pentylenetetrazol seizure threshold are mediated via an interaction with peripheraltype benzodiazepine binding sites.