Brown G B, Gaupp J E, Olsen R W
Neuropsychiatry Research Program, University of Alabama, Birmingham 35294.
Mol Pharmacol. 1988 Jul;34(1):54-9.
Pyrethroid insecticides are synthetic neurotoxins patterned after the naturally occurring pyrethrins. Their mechanism of action is thought to involve effects primarily at the voltage-sensitive sodium channel of both insect and mammalian neurons, although recent studies have raised the possibility that these compounds may also act at the gamma-aminobutyric acid receptor-chloride ionophore complex. Here we show that active pyrethroids of the alpha-cyano-3-phenoxybenzyl class allosterically enhance the binding of [3H]batrachotoxinin-A 20-alpha-benzoate to voltage-sensitive sodium channels of rat brain in a dose-dependent and stereospecific manner. Comparison of the rank order of potency for enhancement of [3H]batrachotoxinin-A 20-alpha-benzoate binding and insecticidal activity in a series of toxic stereoisomers of cypermethrin, representative of the class, reveals a correlation between the two measures. These results support a sodium channel site model for pyrethroid action and suggest a useful and practical method to help evaluate the relationship between effects at the sodium channel and insecticidal potency for members of this class of compounds.
拟除虫菊酯类杀虫剂是模仿天然除虫菊素合成的神经毒素。其作用机制被认为主要涉及对昆虫和哺乳动物神经元电压敏感钠通道的影响，不过最近的研究提出这些化合物也可能作用于γ-氨基丁酸受体-氯离子载体复合物。在此我们表明，α-氰基-3-苯氧基苄基类的活性拟除虫菊酯以剂量依赖性和立体特异性方式变构增强[³H]蛙毒素-A 20-α-苯甲酸酯与大鼠脑电压敏感钠通道的结合。在该类代表性化合物氯氰菊酯的一系列有毒立体异构体中，比较[³H]蛙毒素-A 20-α-苯甲酸酯结合增强的效价顺序与杀虫活性，发现这两种测量结果之间存在相关性。这些结果支持拟除虫菊酯作用的钠通道位点模型，并提出一种有用且实用的方法，以帮助评估该类化合物成员在钠通道上的作用与杀虫效力之间的关系。
