Buckingham_1995_Neuropharmacol_34_591

Nine nitromethylene analogues were tested for their actions on insect neuronal nicotinic acetylcholine receptors (nAChRs). Microelectrode recordings were used to study the actions of nitromethylenes on the cell body of an identified cockroach (Periplaneta americana) motor neurone, the fast coxal depressor (Df) in the metathoracic ganglion. Six nitromethylenes showed potent nAChR agonist actions; others were without nAChR agonist actions. Five nitromethylenes competitively displaced bound [125I]-alpha-bungarotoxin from cockroach nervous system membranes. The rank orders of potency for the compounds determined by their depolarizing actions and their ability to displace [125I]-alpha-bungarotoxin binding were similar. These findings, together with toxicity data obtained on the insects, Nephotettix cinciteps and Nilaparvata lugens, support the hypothesis that insect nAChRs are molecular targets of nitromethylene insecticides. Structure-activity relationships of the nitromethylenes suggest that optimal activity at neuronal nAChRs requires the presence of an electron-withdrawing component in the region of the aryl substituent and an electron-donating component at the 3' position of the imidazolidine ring.