Clark_1997_Pestic.Biochem.Physiol_57_235

In reflecting upon insecticides and their use, it is easy to dwell on their well-documented problems as environmental pollutants and nontarget toxicants. Yet very few chemical industries have been as responsive or as innovative as the agrochemical companies in providing society with new and novel compounds that have allowed us to produce and protect the high quality food and fiber necessary to feed and clothe an ever increasing human population. Given the effectiveness and wide-spread use of insecticides, it was naive not to have envisioned the environmental impacts that these chemicals have caused. Nevertheless, the impacts of insecticide use have resulted in a much more complete and rigorous understanding of the toxicokinetics and toxicodynamics of environmental contaminants, their environmental fate and degradative processes, and an increased insight on mechanisms leading to acquired drug tolerance and resistance. Such understanding would certainly not have been possible without the explicit structure-activity relationships provided by insecticidal chemicals. The availability of homologous series of insecticidal analogues, toxic and nontoxic insecticidal enantiomers, and radiolabeled insecticides have provided us with invaluable tools in the elucidation of how insecticides bind receptors and ultimately produce their toxic response. Pesticide science owes a debt of gratitude to the agrochemical industry for making these compounds readily available to environmental researchers and academic scientists alike. In this review, I examine the mode of action studies of three structurally dissimilar insecticides on the nervous system. These insecticides are DDT, a chlorinated aromatic hydrocarbon that acts as a nerve toxin by modifying the kinetics of voltage-dependent ion channels associated with the neurolemma; deltamethrin, a synthetic pyrethrin analog that acts in a similar fashion as DDT; and azinphosmethyl, a phosphorodithioate organophosphate that acts as nerve toxin by competitively inhibiting acetylcholinesterase (Fig. 1). The activity of these insecticides are assessed using three functional assays: (i) the enhanced release of neurotransmitters from isolated presynaptic nerve terminals; (ii) the behavioral and mortality responses of the ciliate organism,Paramecium;and (iii) the inhibition of acetylcholinesterase associated with azinphosmethyl resistance in Colorado potato beetle. In each case, I summarize our findings in terms of the future benefit that they may provide.