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A novel oxadiazine insecticide is bioactivated in lepidopteran larvae
Author(s) -
Wing Keith D.,
Schnee Michael E.,
Sacher Matthew,
Connair Michael
Publication year - 1998
Publication title -
archives of insect biochemistry and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 66
eISSN - 1520-6327
pISSN - 0739-4462
DOI - 10.1002/(sici)1520-6327(1998)37:1<91::aid-arch11>3.0.co;2-5
Subject(s) - manduca sexta , piperonyl butoxide , biology , biochemistry , sodium channel , pharmacology , malpighian tubule system , metabolite , midgut , chemistry , sodium , larva , botany , organic chemistry , pesticide , agronomy
DPX‐JW062 is a new insecticide showing strong field activity, especially on Lepidoptera. Metabolism studies in several lepidopteran larvae show that orally administered [ 14 C]DPX‐JW062 is rapidly cleaved to a decarbomethoxyllated metabolite (DCJW), based upon HPLC and mass spectrometry identification. The metabolic conversion is correlated with appearance of neurotoxic symptoms. Tissue localization studies with fifth instar Manduca sexta larvae have shown that the fat body and especially midgut are the most active tissues in catalyzing the conversion. The enzyme(s) appears to be localized in many subcellular fractions and can be inhibited by the esterase inhibitors DFP, paraoxon, and DEF but not by the cytochrome p450–dependent monooxygenase inhibitors piperonyl butoxide and 1‐phenyl imidazole, or the glutathione S‐transferase inhibitor N‐ethyl maleimide. The enzyme thus appears to have properties like an esterase/amidase. DCJW is a highly potent blocker of sodium channels in a Manduca sexta larval motor nerve preparation in vitro. The block of compound action potentials in this preparation is voltage‐dependent, which is similar to the local anesthetic‐like action previously ascribed to dihydropyrazole insecticides. In contrast, DPX‐JW062 is weakly active in these blocking actions. We also observe a diminution of spontaneous CNS action potentials which is correlated with neurotoxic symptoms in DPX‐JW062–treated larvae. This mode of action is entirely distinct from pyrethroids, which cause prolonged membrane depolarization leading to repetitive nerve firing. In summary, DPX‐JW062 appears to be rapidly bioactivated by target insects to the potent insecticidally active sodium channel blocker, the S‐enantiomer of its decarbomethoxyllated metabolite. Arch. Insect Biochem. Physiol. 37:91–103, 1998. © 1998 Wiley‐Liss, Inc.