Casida_2011_J.Agric.Food.Chem_59_2762

The safe and effective use of pesticides requires knowledge of their mode of action in pests and adverse effects in nontarget organisms coupled with an understanding of their metabolic activation and detoxification. The author and his laboratory colleagues were privileged to observe, participate in, and sometimes influence these developments for the past six decades. This review considers contributions of the Berkeley and Madison laboratories to understanding insecticides acting at voltage-gated sodium and GABA-gated chloride channels and the nicotinic receptor and at serine hydrolases and other targets as well as the action of insecticide synergists and selected herbicides and fungicides. Some of the discoveries gave new probes, radioligands, photoaffinity labeling reagents, and understanding of reactive intermediates that changed the course of pesticide investigations and related areas of science. The importance of coupling mode of action with metabolism and design with serendipity is illustrated with a wide variety of chemotypes.