Acetylcholine Receptors as Sites for Developing Neonicotinoid Insecticides

Abstract

The world market for insecticides is still dominated, albeit declining, by compounds that irreversibly inhibit acetylcholinesterase (AChE), one of the most essential enzymes in the central nervous system of insects, responsible for the cleavage of the all-important neurotransmitter acetylcholine (Pittman 1971). However, as shown in Table 1, the market share of these AChE inhibitors, i.e. organophosphates and carbamates, decreased from 71% in 1987 to some 56% in 1997. Combining the AChE inhibitors and those insecticides that act on the voltage-gated sodium channel, in particular the pyrethroids, accounts for more than 75% of the world market only by these two modes of action (Table 1). One of the insecticide molecular target sites of growing importance is the nicotinic acetylcholine receptor (nAChR; Table 1); increasing considerably in value over the last decade. Only ten years ago insecticides that acted on the nAChR were of minor economic importance (<2% of the total insecticide market until 1991), and registered compounds were cartap (1964), bensultap (1968) and thiocyclam (1977). These compounds were metabolised in the insect’s body to nereistoxin, a naturally occurring toxin described in the marine worm Lumbriconereis heteropoda.