Correlations between in Vitro and in Vivo Mechanisms of Pyrethroid Insecticide Action

Abstract

Correlations between in Vitro and in Vivo Mechanisms of Pyrethroid Insecticide Action. GAMMON, D. W. (1985). Fundam. Appl. Toxicol. 5, 9–23. Classical neuropharmacological procedures have been used to elucidate insecticide mode of action in vitro. A good deal has thus been learned about pyrethroids but novel techniques have been necessary to explain the toxicology and symptomology. The free-walking, electrode-implanted cockroach technique, which was developed for this purpose, is described. It enabled correlations to be made between symptomology and effects on specific nerves. The negative temperature coefficient of toxicity of allethrin (the first pyrethroid) was explained in terms of repetitive firing in peripheral (sensory) nerves rather than by nerve blockage, which had been suggested from previous in Vitro studies. The elucidation of target sites in vivo and the most useful parameter to study, i.e., repetitive firing in nerve axons, enabled the definition of a pyrethroid resistance mechanism in a major insect pest. It also showed two modes of action for permethrin and cypermethrin, its α-cyano analog. A structure-activity relationship for a range of pyrethroids, combining in Vitro and in Vivo approaches, confirmed two distinct types of pyrethroid action. Studies of poisoning signs and nerve disruptions in Vivo in the mouse and cockroach, using diazepam in conjunction with pyrethroids, implicated the GABA-receptor complex as a target for α-CN-phenoxybenzyl pyrethroids. This was confirmed by making conductance measurements in crayfish claw opener muscle fibers in Vitro.