{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:25:25Z","timestamp":1788265525059,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ionotropic \u03b3\u2010aminobutyric acid receptor (GABAR) is a major inhibitory neurotransmitter receptor in the insect central nervous system and a proven target for multiple classes of insecticides. The recent discovery of the NAM binding site located at the transmembrane subunit interface has revitalized interest in this classic target, leading to the development of two novel classes of insecticides\u2014isoxazolines and meta\u2010diamides\u2014that offer potent efficacy and lack cross\u2010resistance with conventional agents. This review provides a comprehensive overview of the molecular basis of insect GABARs, including subunit composition, gating mechanisms, and the structural pharmacology of distinct binding sites, with an emphasis on the NAM site. We highlight key advances in understanding the mode of action, resistance mechanisms, and structure\u2013activity relationships of NAM inhibitors, and critically evaluate their future potential. A central challenge for this class of insecticides remains their generally high toxicity to honeybee pollinators, which we argue is an inherent consequence of the high sequence conservation of the RDL subunit between pests and beneficial insects. Strategies for mitigating bee toxicity while retaining insecticidal potency are discussed. \u00a9 2026 Society of Chemical Industry.<\/jats:p>","DOI":"10.1002\/ps.71263","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:09:26Z","timestamp":1788264566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the\n                    <scp>GABA<\/scp>\n                    receptor for agricultural Pest control: from molecular mechanisms to novel\n                    <scp>NAM<\/scp>\n                    site inhibitors"],"prefix":"10.1002","author":[{"given":"Zhaokai","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Center for Research and Development of Fine Chemicals Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0059-7316","authenticated-orcid":false,"given":"Yongfu","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Plant Protection Shanxi Agricultural University  Taigu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Center for Research and Development of Fine Chemicals Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Center for Research and Development of Fine Chemicals Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Center for Research and Development of Fine Chemicals Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-0280","authenticated-orcid":false,"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticides, Center for Research and Development of Fine Chemicals Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/imt2.70129","article-title":"Navigating the future of nano\u2010pesticides: a perspective on design, efficacy, mechanisms, and environmental stewardship","volume":"5","author":"Deng XL","year":"2026","journal-title":"iMeta"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.pestbp.2014.11.014","article-title":"IRAC: mode of action 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