Cordova Daniel, Benner Eric A, Schroeder Mark E, Holyoke Caleb W, Zhang Wenming, Pahutski Thomas F, Leighty Robert M, Vincent Daniel R, Hamm Jason C
DuPont Crop Protection, Stine Haskell Research Center, 1090 Elkton Road, Newark, DE 19714, USA.
DuPont Crop Protection, Stine Haskell Research Center, 1090 Elkton Road, Newark, DE 19714, USA.
Insect Biochem Mol Biol. 2016 Jul;74:32-41. doi: 10.1016/j.ibmb.2016.04.008. Epub 2016 Apr 26.
Triflumezopyrim, a newly commercialized molecule from DuPont Crop Protection, belongs to the novel class of mesoionic insecticides. This study characterizes the biochemical and physiological action of this novel insecticide. Using membranes from the aphid, Myzus persicae, triflumezopyrim was found to displace (3)H-imidacloprid with a Ki value of 43 nM with competitive binding results indicating that triflumezopyrim binds to the orthosteric site of the nicotinic acetylcholine receptor (nAChR). In voltage clamp studies using dissociated Periplaneta americana neurons, triflumezopyrim inhibits nAChR currents with an IC50 of 0.6 nM. Activation of nAChR currents was minimal and required concentrations ≥100 μM. Xenopus oocytes expressing chimeric nAChRs (Drosophila α2/chick β2) showed similar inhibitory effects from triflumezopyrim. In P. americana neurons, co-application experiments with acetylcholine reveal the inhibitory action of triflumezopyrim to be rapid and prolonged in nature. Such physiological action is distinct from other insecticides in IRAC Group 4 in which the toxicological mode of action is attributed to nAChR agonism. Mesoionic insecticides act via inhibition of the orthosteric binding site of the nAChR despite previous beliefs that such action would translate to poor insect control. Triflumezopyrim is the first commercialized insecticide from this class and provides outstanding control of hoppers, including the brown planthopper, Nilaparvata lugens, which is already displaying strong resistance to neonicotinoids such as imidacloprid.
三氟甲吡嘧磺隆是杜邦作物保护公司新上市的一种分子，属于新型的中离子型杀虫剂。本研究对这种新型杀虫剂的生化和生理作用进行了表征。使用桃蚜的膜，发现三氟甲吡嘧磺隆能取代（3）H-吡虫啉，其Ki值为43 nM，竞争结合结果表明三氟甲吡嘧磺隆与烟碱型乙酰胆碱受体（nAChR）的正构位点结合。在使用美洲大蠊离体神经元的电压钳研究中，三氟甲吡嘧磺隆抑制nAChR电流，IC50为0.6 nM。nAChR电流的激活最小，所需浓度≥100 μM。表达嵌合nAChRs（果蝇α2/鸡β2）的非洲爪蟾卵母细胞对三氟甲吡嘧磺隆表现出类似的抑制作用。在美洲大蠊神经元中，与乙酰胆碱的共同应用实验表明三氟甲吡嘧磺隆的抑制作用本质上是快速且持久的。这种生理作用与IRAC第4组中的其他杀虫剂不同，后者的毒理学作用方式归因于nAChR激动作用。尽管之前认为这种作用会导致较差的昆虫防治效果，但中离子型杀虫剂通过抑制nAChR的正构结合位点起作用。三氟甲吡嘧磺隆是该类中首个商业化的杀虫剂，对包括褐飞虱Nilaparvata lugens在内的稻飞虱具有出色的防治效果，而褐飞虱已对吡虫啉等新烟碱类杀虫剂表现出很强的抗性。
