RELEVANCE OF [H-3] IMIDACLOPRID BINDING-SITE IN HOUSE-FLY HEAD ACETYLCHOLINE-RECEPTOR TO INSECTICIDAL ACTIVITY OF 2-NITROMETHYLENE-IMIDAZOLIDINES AND 2-NITROIMINO-IMIDAZOLIDINES

Twenty 2-nitromethylene- and 2-nitroimino-imidazolidines and their analogs were examined as inhibitors of [3H]imidacloprid binding in the acetylcholine receptor of house fly head membranes and as knockdown agents for injected house flies pretreated with O-propyl O-(2-propynyl) phenylphosphonate as a synergist. The potency for inhibiting [3H]imidacloprid binding is generally a good predictor (with three exceptions) of the intrinsic neurotoxicity measured as knockdown effect (r = 0.84, n = 17). The six most potent inhibitors have IC50 values of 0.37 to 0.63 nM and KD50 values of 0.004 to 0.058 μg/g. Optimal activity requires the following substituents for the imidacloprid analogs studied: 1-(6-methyl- or 6-chloro-3-pyridinyl)methyl or 1-(2-chloro-5-thiazolyl)methyl; NH, O, S, or CH2, but not NCH3, for the 3-substituent and CHNO2 or NNO2 for the 2-substituent of the imidazolidine moiety; one methylene between the pyridinyl and the imidazolidine moiety; tetrahydropyrimidine as an alternative heterocycle. The relatively low topical toxicity of almost all of the compounds to house flies is not attributable to a low affinity target site but instead to poor penetration and oxidative detoxification. [3H]imidacloprid is an excellent probe for examining this toxicologically relevant binding site for an important new class of insecticides. © 1993 Academic Press.