{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:08Z","timestamp":1785387608128,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"abstract":"Abstract<\/jats:title>\n \n BACKGROUND<\/jats:title>\n The widely\u2010used acaricide pyridaben is classified as a mitochondrial complex I inhibitor (IRAC Group 21). However, a persistent disconnect exists, as it induces acute neuro\u2010excitatory symptoms including ataxia, tremors, leg paralysis and wing buzzing that are phenotypically inconsistent with a purely metabolic mode\u2010of\u2010action but hallmark cholinergic poisoning. This mechanistic ambiguity complicates resistance prediction and obscures the true sublethal hazard to nontarget arthropods. We therefore tested the hypothesis that its documented sublethal neurotoxicity is driven by direct, off\u2010target inhibition of acetylcholinesterase (AChE) and characterized the mode of this inhibition.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Sublethal pyridaben exposure (LC\n 20<\/jats:sub>\n \u2009=\u20095.2\u2009\u03bcg\u2009mL\n \u22121<\/jats:sup>\n ; LC\n 30<\/jats:sub>\n \u2009=\u20098.2\u2009\u03bcg\u2009mL\n \u22121<\/jats:sup>\n ) in\n Drosophila melanogaster<\/jats:italic>\n caused significant neurobehavioral impairment, including 58% reduced locomotion and abolished olfactory attraction with response index declining from +0.50 to \u22120.20.\n In vitro<\/jats:italic>\n , pyridaben acted as a competitive AChE inhibitor (mean inhibitory concentration IC\n 50<\/jats:sub>\n \u2009=\u20099.8\u2009\u00b1\u20091.2\u2009\u03bc\n m<\/jats:sc>\n ; inhibitory\n K<\/jats:italic>\n \u1d62\u2009=\u20097.2\u2009\u00b1\u20090.8\u2009\u03bc\n m<\/jats:sc>\n ;\n n<\/jats:italic>\n \u2009=\u20096 replicates). Critically,\n ex vivo<\/jats:italic>\n analysis of exposed flies confirmed dose\u2010dependent AChE inhibition (29% reduction at LC\n 20<\/jats:sub>\n ; 46% reduction at LC\n 30<\/jats:sub>\n ), concurrent with behavioral deficits, demonstrating\n in vivo<\/jats:italic>\n target engagement. This mechanism was conserved in the agriculturally significant pest\n Drosophila suzukii<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n Competitive AChE inhibition is a novel secondary mechanism contributing to pyridaben's sublethal neurotoxicity. These findings resolve the toxicological paradox of its symptomology and provide a mechanistic basis for understanding behavioral impairment in exposed insects, with implications for refining diagnostic resistance monitoring approaches and informing mechanism\u2010based insecticide rotation strategies for sustainable pest management. \u00a9 2026 Society of Chemical Industry.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ps.71149","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:35:32Z","timestamp":1785386132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Competitive\n AChE<\/scp>\n inhibition: a novel secondary mechanism driving pyridaben's sublethal neurotoxicity"],"prefix":"10.1002","author":[{"given":"Fahd A","family":"Al\u2010Mekhlafi","sequence":"first","affiliation":[{"name":"Department of Zoology, College of Science King Saud University Riyadh Saudi 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A","family":"Wadaan","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0323653","article-title":"Yeast\u2010based attract\u2010and\u2010kill strategies for Drosophila suzukii management without disrupting honey bee activity","volume":"20","author":"Dum\u00e9nil C","year":"2025","journal-title":"PLoS One"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/ps.4348","article-title":"Toxicities and effects of insecticidal toxic baits to control Drosophila suzukii and Zaprionus indianus (Diptera: Drosophilidae)","volume":"73","author":"Andreazza F","year":"2017","journal-title":"Pest Manag Sci"},{"key":"e_1_2_10_4_1","article-title":"Advances in the management of 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