Flonicamid metabolite 4-trifluoromethylnicotinamide is a chordotonal organ modulator insecticide†

BACKGROUND The selective aphicide flonicamid is known to cause symptoms in aphids that are like those of chordotonal organ TRPV channel modulator insecticides such as pymetrozine, pyrifluquinazon and afidopyropen. Flonicamid is classified by the Insecticide Resistance Action Committee as a chordotonal organ modulator with an undefined target site. However, although it has been shown not to act on TRPV channels, flonicamid's action on chordotonal organs has not been documented in the literature. RESULTS Flonicamid causes locusts to extend their hindlegs, indicating an action on the femoral chordotonal organ. In fruit flies, it abolishes negative gravitaxis behavior by disrupting transduction and mechanical amplification in antennal chordotonal neurons. Although flonicamid itself only weakly affects locust chordotonal organs, its major animal metabolite 4-trifluoromethylnicotinamide (TFNA-AM) potently stimulates both locust and fly chordotonal organs. Like pymetrozine, TFNA-AM rapidly increases Ca2+ in antennal chordotonal neurons in wild-type flies, but not iav(1) mutants, yet the effect is nonadditive with the TRPV channel agonist. CONCLUSIONS Flonicamid is a pro-insecticide form of TFNA-AM, a potent chordotonal organ modulator. The functional effects of TFNA-AM on chordotonal organs of locusts and flies are indistinguishable from those of the TRPV agonists pymetrozine, pyrifluquinazon and afidopyropen. Because our previous results indicate that TFNA-AM does not act directly on TRPV channels, we conclude that it acts upstream in a pathway that leads to TRPV channel activation. (c) 2022 Society of Chemical Industry.

Automated summary

The selective aphicide flonicamid has been found to affect the femoral chordotonal organ in locusts and disrupt the transduction and mechanical amplification in antennal chordotonal neurons in fruit flies. Its major metabolite, 4-trifluoromethylnicotinamide (TFNA-AM), also stimulates chordotonal organs in both locusts and flies. These effects are similar to those of TRPV agonists pymetrozine, pyrifluquinazon, and afidopyropen.