Antagonism of a neonicotinoid insecticide imidacloprid at neuromuscular receptors.

We investigated interactions of the neonicotinoid insecticide imidacloprid with the nicotinic acetylcholine-regulated receptors (nAcChR) of embryonic frog muscle cells. The response of the muscle cells to acetylcholine, nicotine and imidacloprid was monitored as cell contractions. Acetylcholine was more potent than nicotine (EC(50)=5×10(-8)M versus 6×10(-7)M) in this physiological test system. Contractions induced by acetylcholine or nicotine were both blocked by α-bungarotoxin (IC(50)=9×10(-7)M). Imidacloprid itself did not cause cell contractions but at concentrations ≥3.3×10(-6)M prevented or attenuated those induced by acetylcholine (5×10(-7)M and 5×10(-5)M) or nicotine (5×10(-6)M to 5×10(-3)M). The dose response relationship between acetylcholine or nicotine, imidacloprid and cell contractions suggests that imidacloprid is an antagonist at the nAcChR of the muscle cells in contrast to its established role as an agonist in its toxic action on insect neural receptors. In chicken embryos, imidacloprid caused arthrogryposis, presumably due to its interference with the embryonic neuromuscular nAcChR. A magnitude of imidacloprid dose that caused arthrogryposis indicates a negligible teratogenic potential of imidacloprid when applied for the insect pest control.