Buckingham S D, Balk M L, Lummis S C, Jewess P, Sattelle D B
Babraham Institute Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, U.K.
Neuropharmacology. 1995 Jun;34(6):591-7. doi: 10.1016/0028-3908(95)00024-z.
Nine nitromethylene analogues were tested for their actions on insect neuronal nicotinic acetylcholine receptors (nAChRs). Microelectrode recordings were used to study the actions of nitromethylenes on the cell body of an identified cockroach (Periplaneta americana) motor neurone, the fast coxal depressor (Df) in the metathoracic ganglion. Six nitromethylenes showed potent nAChR agonist actions; others were without nAChR agonist actions. Five nitromethylenes competitively displaced bound [125I]-alpha-bungarotoxin from cockroach nervous system membranes. The rank orders of potency for the compounds determined by their depolarizing actions and their ability to displace [125I]-alpha-bungarotoxin binding were similar. These findings, together with toxicity data obtained on the insects, Nephotettix cinciteps and Nilaparvata lugens, support the hypothesis that insect nAChRs are molecular targets of nitromethylene insecticides. Structure-activity relationships of the nitromethylenes suggest that optimal activity at neuronal nAChRs requires the presence of an electron-withdrawing component in the region of the aryl substituent and an electron-donating component at the 3' position of the imidazolidine ring.
对九种硝基亚甲基类似物进行了测试，以研究它们对昆虫神经元烟碱型乙酰胆碱受体（nAChRs）的作用。采用微电极记录法，研究硝基亚甲基对已鉴定的蟑螂（美洲大蠊）运动神经元（后胸神经节中的快速髋屈肌（Df））细胞体的作用。六种硝基亚甲基表现出强效的nAChR激动剂作用；其他的则没有nAChR激动剂作用。五种硝基亚甲基竞争性地从蟑螂神经系统膜中置换结合的[125I] -α-银环蛇毒素。由其去极化作用和置换[125I] -α-银环蛇毒素结合的能力所确定的化合物效力等级顺序相似。这些发现，连同在昆虫黑尾叶蝉和褐飞虱上获得的毒性数据，支持了昆虫nAChRs是硝基亚甲基杀虫剂分子靶标的假说。硝基亚甲基的构效关系表明，在神经元nAChRs上的最佳活性需要在芳基取代基区域存在吸电子基团以及在咪唑烷环的3'位存在供电子基团。
