Correlations betweenin Vitroandin VivoMechanisms 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 actionin 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 previousin Vitrostudies. The elucidation of target sitesin vivoand 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, itsα-cyano analog. A structure-activity relationship for a range of pyrethroids, combiningin Vitroandin Vivoapproaches, confirmed two distinct types of pyrethroid action. Studies of poisoning signs and nerve disruptionsin Vivoin the mouse and cockroach, using diazepam in conjunction with pyrethroids, implicated the GABA-receptor complex as a target forα-CN-phenoxybenzyl pyrethroids. This was confirmed by making conductance measurements in crayfish claw opener muscle fibersin Vi
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