Interaction of dinotefuran and its analogues with nicotinic acetylcholine receptors of cockroach nerve cords

To investigate the action of dinotefuran (MTI‐446, 1‐methyl‐2‐nitro‐3‐(tetrahydro‐3‐furylmethyl)guanidine), a recently developed insecticide, on insect nicotinic acetylcholine receptors (nAChRs), we determined the potencies of the compound and 15 analogues in inhibiting the specific binding of [ 3 H]epibatidine (EPI), a nAChR agonist, and [ 3 H]α‐bungarotoxin (α‐BGT), a competitive nAChR antagonist, to the nerve cord membranes of American cockroaches ( Periplaneta americana ). Racemic dinotefuran inhibited [ 3 H]EPI binding with an IC 50 of 890 n M and [ 3 H]α‐BGT binding with an IC 50 of 36.1 µ M . Scatchard analysis indicated that the dinotefuran inhibition of [ 3 H]EPI binding was a competitive one. Slight structural modification caused a drastic reduction in potency; only four analogues were found to be equipotent to or more potent than dinotefuran. Chloropyridinyl and chlorothiazolyl neonicotinoid insecticides displayed two or three orders of magnitude higher potency than dinotefuran. There was a good correlation between the IC 50 values of tested compounds obtained with [ 3 H]EPI and those obtained with [ 3 H]α‐BGT. A better correlation was observed between 3‐h knockdown activities (KD 50 ) against German cockroaches ( Blattella germanica ) and IC 50 values obtained from [ 3 H]EPI assays than between 24‐h lethal activities (LD 50 ) and IC 50 values. While the results indicate that dinotefuran and its analogues interact with the ACh‐binding site in cockroach nAChRs, it remains to be elucidated why they displayed lower potencies than those expected based on their insecticidal activities. © 2001 Society of Chemical Industry