The novel pyridazine pyrazolecarboxamide insecticide dimpropyridaz inhibits chordotonal organ function upstream of TRPV channels

• Published in: Pest management science Vol. 79; no. 5; pp. 1635 - 1649
• Main Authors: Spalthoff, Christian, Salgado, Vincent L., Balu, Narayanan, David, Michael D., Hehlert, Philip, Huang, Huazhang, Jones, John E., Kandasamy, Ramani, Knudsen, Gabriel A., Lelito, Katherine R., Machamer, James B., Nesterov, Alexandre, Tomalski, Michael, Wahl, Gregory D., Wedel, Barbara J., Göpfert, Martin C.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.2023; Wiley Subscription Services, Inc
• Subjects: Afidopyropen; Amides - pharmacology; Animals; Aphidoidea; Aphids; Bemisia tabaci; calcium; Calcium (intracellular); Calcium ions; Channels; Chordotonal organ; Dealkylation; Drosophila melanogaster; flonicamid; Insecta; Insecticide Resistance; Insecticides; Insecticides - pharmacology; Insects; mechanism of action; Metabolites; Mode of action; Neurons; nicotinamide; Periplaneta americana; Pest control; Pests; Piercing; PPC; pymetrozine; Pyridazines; pyrifluquinazon; resistance management; Transient receptor potential proteins; transient receptor potential vanilloid channels; Upstream; Periplaneta americana; pyrifluquinazon; Afidopyropen; PPC; Bemisia tabaci; nicotinamide; flonicamid; pymetrozine; Drosophila melanogaster
• ISSN: 1526-498X; 1526-4998; 1526-4998
• DOI: 10.1002/ps.7352

BACKGROUND Pyridazine pyrazolecarboxamides (PPCs) are a novel insecticide class discovered and optimized at BASF. Dimpropyridaz is the first PPC to be submitted for registration and controls many aphid species as well as whiteflies and other piercing–sucking insects. RESULTS Dimpropyridaz and other tertiary amide PPCs are proinsecticides that are converted in vivo into secondary amide active forms by N‐dealkylation. Active secondary amide metabolites of PPCs potently inhibit the function of insect chordotonal neurons. Unlike Group 9 and 29 insecticides, which hyperactivate chordotonal neurons and increase Ca2+ levels, active metabolites of PPCs silence chordotonal neurons and decrease intracellular Ca2+ levels. Whereas the effects of Group 9 and 29 insecticides require TRPV (Transient Receptor Potential Vanilloid) channels, PPCs act in a TRPV‐independent fashion, without compromising cellular responses to Group 9 and 29 insecticides, placing the molecular PPC target upstream of TRPVs. CONCLUSIONS PPCs are a new class of chordotonal organ modulator insecticide for control of piercing–sucking pests. Dimpropyridaz is a PPC proinsecticide that is activated in target insects to secondary amide forms that inhibit the firing of chordotonal organs. The inhibition occurs at a site upstream of TRPVs and is TRPV‐independent, providing a novel mode of action for resistance management. © 2023 BASF Corporation. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Dimpropyridaz provides a novel mode of action for the control of piercing–sucking insects, acting on a new target in the chordotonal organ upstream of transient receptor potential vanilloid (TRPV) channels and different from the target of flonicamid, an inhibitor of nicotinamide amidase (NAAM). Nicotinamide and Insecticide Resistance Action Committee Group 9 insecticides modulate TRPV channels.