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

Gabriel Arther Knudsen; Christian Spalthoff; R Valdes Salgado; Narayanan Balu; DE David; Philip Hehlert; H Huang; John Jones; Ramani Kandasamy; Gabe Knudsen; Katherine R Lelito; James B Machamer; Alexandre Nesterov; Michael Tomalski; Gregory D Wahl; Barbara Wedel; Martin C Göpfert

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

Spalthoff, C., Salgado, V. L., Balu, N., David, M. D., Hehlert, P., Huang, H., Jones, J. E., Kandasamy, R., Knudsen, G. A., Lelito, K. R., Machamer, J. B., Nesterov, A., Tomalski, M., Wahl, G. D., Wedel, B. J., & Göpfert, M. C. (2023). The novel pyridazine pyrazolecarboxamide insecticide dimpropyridaz inhibits chordotonal organ function upstream of TRPV channels. Pest Management Science, 79(5), 1635-1649. https://doi.org/10.1002/ps.7352

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Abstract

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.