Molecular Mechanism of Action of Cycloxaprid, An Oxabridged -Nitromethylene Neonicotinoid.

Cycloxaprid, an oxabridged -nitromethylene neonicotinoid, showed high insecticidal activity in Hemipteran insect pests. In this study, the action of cycloxaprid was characterized by recombinant receptor Nlα1/rβ2 and cockroach neurons. On Nlα1/β2 in oocytes, cycloxaprid acted as a full agonist. The imidacloprid resistance-associated mutation Y151S reduced the of cycloxaprid by 37.0% and increased values by 1.9-fold, while the of imidacloprid was reduced by 72.0%, and values increased by 2.3-fold. On cockroach neurons, the maximum currents elicited by cycloxaprid were only 55% of that of acetylcholine, a full agonist, but with close values of that of -neonicotinoids. In addition, cycloxaprid inhibited acetylcholine-evoked currents on insect neurons in a concentration-dependent manner when co-applied with acetylcholine. Cycloxaprid at low concentrations significantly inhibited the activation of nAChRs by acetylcholine, and its inhibition potency at 1 µM was higher than its activation potency on insect neurons. Two action potencies, activation, and inhibition, by cycloxaprid on insect neurons provided an explanation for its high toxicity to insect pests. In summary, as a -nitromethylene neonicotinoid, cycloxaprid showed high potency on both recombinant nAChR Nlα1/β2 and cockroach neurons, which guaranteed its high control effects on a variety of insect pests.