Insect nicotinic acetylcholine receptor: Conserved neonicotinoid specificity of [H-3]imidacloprid binding site

The insect nicotinic acetylcholine receptor (nAChR) is a major target for i nsecticide action. The rapidly expanding use of neonicotinoid insecticides of varied structures makes it increasingly important to define similarities and differences in their action, particularly for the first-generation chl oropyridinyl compounds versus the second-generation chlorothiazolyl derivat ives. We have shown with Musca domestica that a convenient and relevant det ermination of the neonicotinoid insecticide target is a binding site assay with [H-3]imidacloprid (H-3]IMI), This study uses membranes from the aphids Myzus persicae and Aphis craccivora and from heads of the flies Drosophila melanogaster and Musca domestica to characterize the [H-3]IMI binding site s relative to their number and possible species variation in structure-acti vity relationships, With emphasis on commercial neonicotinoids, six potent chloropyridinyl compounds are compared with the corresponding six chlorothi azolyl analogues (syntheses are given for chemicals prepared differently th an previously described). The preference for chloropyridinyl versus chlorot hiazolyl is not dependent on the insect species examined but instead on oth er structural features of the molecule, The chlorothiazolyl substituent gen erally confers higher potency in the clothianidin and desmethylthiamethoxam series and the chloropyridinyl moiety in the imidacloprid, thiacloprid, ac etamiprid, and nitenpyram series. Two chlorothiazolyl compounds compete dir ectly with the chloropyridinyl [H-3]IMI for the same binding sites in Myzus and Drosophila membranes. This study shows conserved neonicotinoid specifi city of the [H-3]IMI binding site in each of the four insect species examin ed.