PK 11195 antagonism of pyrethroid-induced proconvulsant activity.
The acute administration of 1R,cis, alpha S-cypermethrin, deltamethrin fenvalerate and permethrin produced a dose-dependent lowering of the dose of pentylenetetrazol required to elicit a seizure in rats. The proconvulsant action of cypermethrin displayed stereospecificity in that the 1R, cis, alpha S isomer of cypermethrin was the most potent compound tested, while the non-insecticidal isomer, 1S,cis, alpha R-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 peripheral-type benzodiazepine binding sites.
L L
LL
Devaud
P
P
Szot
T F
TF
Murray
D000818:Animals; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009570:Nitriles; D010433:Pentylenetetrazole / Q000633:toxicity; D026023:Permethrin; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013237:Stereoisomerism
D003292:Convulsants; D007546:Isoquinolines; D009570:Nitriles; D011722:Pyrethrins; C017160:cypermethrin; C017180:decamethrin; D026023:Permethrin; D010433:Pentylenetetrazole; C037850:PK 11195; C017690:fenvalerate