Wolstenholme Adrian J
Department of Infectious Diseases and Center for Tropical and Emerging Global Disease, University of Georgia, Athens, GA 30602, USA.
Invert Neurosci. 2010 Nov;10(1):5-10. doi: 10.1007/s10158-010-0105-y. Epub 2010 Oct 15.
Avermectins and milbemycins are an important family of anthelmintics, insecticides and acaricides. Their mode of action is as positive allosteric modulators of ligand-gated chloride channels, and at higher concentrations, they gate some channels directly. Though it has long been known that the avermectins do not compete for the ligand binding site, the actual site at which they interact with their receptors has been unclear. Recent data demonstrate the importance to drug binding of amino acid residues predicted to line a water-filled pocket in the channel domain. This pocket acts as the binding site for anaesthetics and other modulators of mammalian GABA(A) and glycine receptors, suggesting similarities in the mode of action between these drugs and the avermectins/milbemycins.
阿维菌素和米尔倍霉素是一类重要的驱虫剂、杀虫剂和杀螨剂。它们的作用方式是作为配体门控氯离子通道的正变构调节剂，在较高浓度下，它们可直接使一些通道开启。尽管长期以来人们都知道阿维菌素并不与配体结合位点竞争，但它们与受体相互作用的实际位点一直不清楚。最近的数据表明，预测位于通道结构域中一个充满水的口袋内的氨基酸残基对药物结合很重要。这个口袋充当哺乳动物γ-氨基丁酸A（GABA(A)）和甘氨酸受体的麻醉剂及其他调节剂的结合位点，这表明这些药物与阿维菌素/米尔倍霉素在作用方式上存在相似性。
