Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA.
Chem Biol Interact. 2013 Mar 25;203(1):221-5. doi: 10.1016/j.cbi.2012.08.002. Epub 2012 Aug 16.
The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use - the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction. Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations. Species selectivity is determined in part by inhibitor and target site specificity. Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity. Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others. Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains. The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10 years ago for several reasons: there have been no major new compounds for 30 years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed. Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system. The OPs and MCs are down but not out.
抗胆堿酯酶（antiChE）有机磷（OP）和氨基甲酸酯（MC）杀虫剂作为接触性和系统性植物保护剂已被非常有效地使用了七十年。大约有 90 种此类化合物仍在使用中 - 是任何杀虫剂化学型或作用方式中数量最多的。在昆虫和哺乳动物中，AChE 抑制和乙酰胆碱积累导致兴奋和死亡。昆虫的膽堿能系统位于中枢（在那里它免受離子化的 OP 和 MC 的影响），但不在神经肌肉接頭處。昆虫和哺乳動物 AChE 之間的結構差異也表現在它們的基因組、氨基酸序列和活性位點構象中。抑制劑和靶位點的特異性決定了物種的選擇性。用 OP 和 MC 對害蟲種群的選擇導致了許多改變了抑制劑特異性的改變的 AChE，其中一些賦予了昆蟲抗藥性，而另一些則提高了敏感性。抗膽堿酯酶殺蟲劑的大部分成功歸功於一系列 CYP450 氧化酶、水解酶、谷胱甘肽 S-轉移酶等的生物活化和解毒的適當平衡。這些酶的已知抑制劑會阻斷解毒作用並增強效力，這在抗性菌株中尤為重要。OP 和 MC 在全球殺蟲劑銷售中的市場份額為 19%，僅為 10 年前的一半，原因有以下幾個方面：30 年來沒有新的主要化合物；抗藥性削弱了它們的有效性；人類毒性問題仍然存在；專利已過期，降低了更新注冊包的動力；替代化學型或控制方法已被開發。盡管有所下降，但它們仍在害蟲防治中發揮著重要作用，對其靶位和代謝的了解不斷增加，可能使設計不敏感的 AChE 抑制劑和靶向膽堿能系統新靶位成為可能。OP 和 MC 正在衰退，但尚未消失。
