title: Novel nicotinic action of the sulfoximine insecticide sulfoxaflor.
abstract: The novel sulfoximine insecticide sulfoxaflor is as potent or more effective than the neonicotinoids for toxicity to green peach aphids (GPA, Myzus persicae). The action of sulfoxaflor was characterized at insect nicotinic acetylcholine receptors (nAChRs) using electrophysiological and radioligand binding techniques. When tested for agonist properties on Drosophila melanogaster Dα2 nAChR subunit co-expressed in Xenopus laevis oocytes with the chicken β2 subunit, sulfoxaflor elicited very high amplitude (efficacy) currents. Sulfoximine analogs of sulfoxaflor were also agonists on Dα2/β2 nAChRs, but none produced maximal currents equivalent to sulfoxaflor nor were any as toxic to GPAs. Additionally, except for clothianidin, none of the neonicotinoids produced maximal currents as large as those produced by sulfoxaflor. These data suggest that the potent insecticidal activity of sulfoxaflor may be due to its very high efficacy at nAChRs. In contrast, sulfoxaflor displaced [(3)H]imidacloprid (IMI) from GPA nAChR membrane preparations with weak affinity compared to most of the neonicotinoids examined. The nature of the interaction of sulfoxaflor with nAChRs apparently differs from that of IMI and other neonicotinoids, and when coupled with other known characteristics (novel chemical structure, lack of cross-resistance, and metabolic stability), indicate that sulfoxaflor represents a significant new insecticide option for the control of sap-feeding insects.
authors.affiliation: Dow AgroSciences, LLC, 9330 Zionsville Rd., Indianapolis, IN 46268, USA. gbwatson@dow.com
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Watson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loso
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Babcock
authors.forename: James M
authors.initials: JM
authors.lastname: Hasler
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Letherer
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Young
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Zhu
authors.forename: John E
authors.initials: JE
authors.lastname: Casida
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Sparks
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects* / Q000502:physiology; D001667:Binding, Competitive; D002645:Chickens; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007300:Insect Control / Q000379:methods*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials; D000073943:Neonicotinoids; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D013457:Sulfur Compounds / Q000494:pharmacology*; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D029721:Drosophila Proteins; D007093:Imidazoles; D019476:Insect Proteins; D007306:Insecticides; D000073943:Neonicotinoids; D018722:Nicotinic Agonists; D009574:Nitro Compounds; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D013457:Sulfur Compounds; C113681:nicotinic acetylcholine receptor alpha-subunits, Drosophila; C082359:imidacloprid; C560328:sulfoxaflor