Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management, University of California, Berkeley, California 94720, USA.
Annu Rev Entomol. 2013;58:99-117. doi: 10.1146/annurev-ento-120811-153645.
Neuroactive insecticides are the principal means of protecting crops, people, livestock, and pets from pest insect attack and disease transmission. Currently, the four major nerve targets are acetylcholinesterase for organophosphates and methylcarbamates, the nicotinic acetylcholine receptor for neonicotinoids, the γ-aminobutyric acid receptor/chloride channel for polychlorocyclohexanes and fiproles, and the voltage-gated sodium channel for pyrethroids and dichlorodiphenyltrichloroethane. Species selectivity and acquired resistance are attributable in part to structural differences in binding subsites, receptor subunit interfaces, or transmembrane regions. Additional targets are sites in the sodium channel (indoxacarb and metaflumizone), the glutamate-gated chloride channel (avermectins), the octopamine receptor (amitraz metabolite), and the calcium-activated calcium channel (diamides). Secondary toxic effects in mammals from off-target serine hydrolase inhibition include organophosphate-induced delayed neuropathy and disruption of the cannabinoid system. Possible associations between pesticides and Parkinson's and Alzheimer's diseases are proposed but not established based on epidemiological observations and mechanistic considerations.
神经活性杀虫剂是保护农作物、人类、牲畜和宠物免受害虫侵袭和疾病传播的主要手段。目前，四大神经靶标分别为有机磷和氨基甲酸酯类的乙酰胆碱酯酶、新烟碱类的烟碱型乙酰胆碱受体、多氯环已烷和氟吡菌胺的γ-氨基丁酸受体/氯离子通道，以及拟除虫菊酯和滴滴涕的电压门控钠离子通道。物种选择性和获得性抗性部分归因于结合亚位、受体亚基界面或跨膜区域的结构差异。其他靶标包括钠离子通道（茚虫威和甲氧虫酰肼）、谷氨酸门控氯离子通道（阿维菌素类）、章鱼胺受体（苯丁锡代谢物）和钙激活钙通道（二酰胺类）。非靶标丝氨酸水解酶抑制引起的哺乳动物的次要毒性作用包括有机磷诱导的迟发性神经病和大麻素系统紊乱。基于流行病学观察和机制考虑，提出了杀虫剂与帕金森病和阿尔茨海默病之间可能存在关联，但尚未得到证实。
