Recent progress in the mechanism of action of insecticides: Pyrethroids, fipronil and indoxacarb

Abstract

The mechanisms of action of pyrethroids, fipronil and indoxacarb on neuroreceptors and ion channels are summarized based primarily on our own studies. The major target site of pyrethroids is the sodium channel, and the toxicity is profoundly amplified from channel modulation to hyperactive symptoms in animals. For tetramethrin, only ~1% of sodium channel population needs to be modified from brief opening to very prolonged opening to cause hyperactivity. Selective toxicity of pyrethroids between mammals and insects can be largely explained on the basis of differential sodium channel sensitivity to pyrethroids and negative temperature dependence of pyrethroid action. Fripronil blocks rat GABAA receptors, and the effect is exerted in both resting and active states of the receptors. It acts on GABA-receptor site different from the picrotoxinin binding site. Cockroach GABA receptors are more sensitive to fipronil blocking action than rat GABAA receptors. Indoxacarb and its metabolite DCJW have multiple actions on sodium channels, neuronal nicotinic acetylcholine receptors, and GABA receptors in both rat and cockroach. However, modulation of these receptors and channels differs considerably between mammals and insects.