A pharmacological study of pyrethroid neurotoxicity in mice

Permethrin (cis-, trans-, and technical grade [tech.]) and deltamethrin, representatives of the non-cyano- and cyano-containing classes of synthetic pyrethroids, produced neurotoxic symptoms when administered to mice. ED₅₀ values for this effect were compared following intracerebroventricular (icv) or peripheral (iv) injection. Both permethrin and deltamethrin showed large increases in potency following icv administration, suggesting a mainly central site of action for both classes of pyrethroid. Pretreatment of mice with drugs affecting central noradrenergic, cholinergic, or serotonergic transmission was demonstrated to potentiate the toxic response to iv injections of tech.-permethrin, while some symptoms of toxicity could be partially alleviated by ip pretreatment with diazepam, aminooxyacetic acid, or cycloheximide.