Bioactivation and mode of action of the oxadiazine indoxacarb in insects

By K. D. Wing, M. Sacher, Yasushi Kagaya, Tsurubuchi Yuji, Laura Mulderig, Michael Connair, M. Schnee. 2000

283 citations recorded by the source corpus.

Abstract DPX-MP062 (indoxacarb) is a novel oxadiazine insecticide which has good field activity against a number of pest Lepidoptera, as well as certain Homoptera and Coleoptera. Indoxacarb (discovered and developed by E.I. DuPont and Co.) is a 75%S : 25%R mixture of enantiomers at the chiral bicyclic carbon; DPX-JW062 is the corresponding racemic compound. Several species of lepidopteran larvae can rapidly metabolize 14 C-JW062 to 14 C-DCJW (for N-decarbomethoxyllated JW062) after ingestion, and more slowly after topical treatment; this conversion is correlated with the appearance of neurotoxic symptoms. Several sucking insects are also capable of absorbing and bioactivating indoxacarb after either dermal or oral administration, but do so much more slowly than the Lepidoptera. DCJW is a highly potent, voltage-dependent blocker of Na + -dependent compound action potentials when tested in a Manduca sexta larval abdominal motoneuron preparation; DPX-JW062 was much less potent in this regard. When larvae were poisoned in vivo, onset of paralysis and block of central nervous system action potentials was more rapid with DCJW than with DPX-JW062; onset of neurotoxic symptoms leads to a rapid and irreversible halt in feeding. The S-enantiomer of DCJW is active both in the motoneuron preparation in vitro and in lepidopteran larvae in vivo; however S-DPX-JW062 is active in vivo only, while the R-enantiomers of DCJW and DPX-MP062 are inactive in both. Thus, activation of the parent oxadiazines to the S-enantiomers of the N -decarbomethoxyllated metabolites, which are powerful sodium channel blockers, is the toxic mechanism of action in Lepidoptera and apparently for other pest insects as well; however, the rate of bioactivation is a critical factor in determining the speed and ultimate toxicity of this compound in different insect species. Indoxacarb's inherent activity against Lepidoptera is comparable to the most potent insecticides ever commercialized.

Subfields: Insect Science, Plant Science

View Paper: https://www.semanticscholar.org/paper/83f0d62c1bbe9eee49bbf220624b972d8a742098

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Citations in the corpus

Indoxacarb resistance in the house fly, Musca domestica (2004, background): “Indoxacarb was moderately toxic to house flies (Table 4) in agreement with previous reports [2,8].”
Side effects of selected insecticides on the Tuta absoluta (Lepidoptera: Gelechiidae) predators Macrolophus pygmaeus and Nesidiocoris tenuis (Hemiptera: Miridae) (2011, background): “In the Mediterranean Basin, two of the most promising biological control agents for T. absoluta are the predators Nesidiocoris tenuis (Reuter) and Macrolophus pygmaeus (Rambur) (Hemiptera: Miridae) (Desneux et al. 2010).”
Metabolomics – A robust bioanalytical approach for the discovery of the modes-of-action of pesticides: A review (2011, background): “On the other hand, metabolomics could provide insights into the bioactivation of insecticides in plants or insects that in many cases determines their toxicity and selectivity [75–77] and which could be misinterpreted by performing experiments using solely the targeted organisms.”
Effects of spinosad and indoxacarb on survival, development, and reproduction of the multicolored Asian lady beetle (Coleoptera: Coccinellidae) (2005, background): “The relatively new insecticides, spinosad and indoxacarb, are eVective against several lepidopteran pests (Burkness et al., 2003; Wing et al., 2000).”
Neuroactive insecticides: targets, selectivity, resistance, and secondary effects. (2013, background): “The oxadiazine indoxacarb is an effective proinsecticide that is enzymatically hydrolyzed to the active agent (77, 147).”