Casida J E
Department of Entomological Sciences, University of California, Berkeley 94720.
Arch Insect Biochem Physiol. 1993;22(1-2):13-23. doi: 10.1002/arch.940220104.
Three billion (3 x 10(9)) pounds of hexachlorocyclohexanes, polychlorobornanes, and chlorinated cyclodienes (such as lindane, toxaphene, and endosulfan, respectively) were used to control pest insects before their mode of action was established as blocking the GABA-gated chloride channel. With the restricted use or demise of these polychlorocycloalkanes (each approximately 50 to approximately 75% by weight of chlorine), the GABAergic system is for now an underutilized target of insecticide action. Newer compounds with outstanding potency at this receptor and as toxicants to houseflies are suitably-substituted 2,6,7-trioxabicyclo[2.2.2]-octanes, particularly the bicycloorthobenzoates, and 1,3-dithianes, including those with no halogenated substituents. Picrotoxinin analogs and alkynylphenyl-silatranes also act at this target but are of lower insecticidal activity. [3H]n-Propyl-ethynylbicycloorthobenzoate ([3H]EBOB) is for now the best radioligand for this insecticidally-relevant binding site in insects. Macrocyclic lactones such as the avermectins and moxidectin act at a different binding site to disrupt chloride flux and they have a different spectrum of insecticidal activity and no cross resistance with cyclodienes in houseflies. The search for new insecticides has provided the incentive and probes for a better understanding of the insect GABAergic system.
在六氯环己烷、多氯硼烷和氯代环二烯（分别如林丹、毒杀芬和硫丹）的作用方式被确定为阻断γ-氨基丁酸（GABA）门控氯离子通道之前，人们曾使用30亿磅（3×10⁹磅）的这些物质来防治害虫。随着这些多氯环烷烃（每种物质的氯含量约为50%至约75%）的使用受到限制或被淘汰，GABA能系统目前是杀虫剂作用中未得到充分利用的靶点。在该受体上具有出色效力且对家蝇有毒性的新型化合物是适当取代的2,6,7-三氧杂双环[2.2.2]辛烷，特别是双环邻苯二甲酸酯，以及1,3-二噻烷，包括那些没有卤代取代基的化合物。印防己毒素类似物和炔基苯基硅氮烷也作用于该靶点，但杀虫活性较低。[³H]正丙基-乙炔基双环邻苯二甲酸酯（[³H]EBOB）目前是用于昆虫中与杀虫相关的该结合位点的最佳放射性配体。大环内酯类如阿维菌素和莫昔克丁作用于不同的结合位点以扰乱氯离子通量，它们具有不同的杀虫活性谱，且在家蝇中与环二烯类没有交叉抗性。对新型杀虫剂的探索为更好地理解昆虫GABA能系统提供了动力和探针。
