Pinnock R D, Sattelle D B, Gration K A, Harrow I D
Department of Zoology, University of Cambridge, U.K.
Neuropharmacology. 1988 Aug;27(8):843-8. doi: 10.1016/0028-3908(88)90101-3.
Intracellular recording and current-clamp techniques were used to investigate the cholinergic activity of the anthelmintics, morantel, pyrantel and levamisole, applied to the fast coxal depressor motorneurone (Df) of the cockroach Periplaneta americana. Application of these agents and acetylcholine to the bath resulted in dose-dependent changes in conductance and corresponding depolarization of the neuronal membrane. Relative potencies of the drugs were determined from dose-response relationships and the rank order of effectiveness was as follows: carbachol much greater than levamisole greater than pyrantel greater than morantel. Evidence that these drugs were acting at the same site of action was obtained with the antagonist, mecamylamine, which abolished the responses to all these agents. It is concluded that the weak insecticidal action of these potent anthelmintics may result in part from their weak cholinergic agonist action on insect neurones, which contrasts with their potent agonist actions on acetylcholine receptors of helminth nerve and muscle tissues. The striking differences in potency on different invertebrate tissues appears to reflect differences in the properties of acetylcholine receptors between insects and nematodes. Further characterization of neurotransmitter receptors in invertebrates is needed in order to facilitate the rational design of broad-spectrum antiparasitic agents with low toxicity in mammals.
采用细胞内记录和电流钳技术，研究了驱虫药莫仑太尔、噻嘧啶和左旋咪唑对美洲大蠊快速髋部降肌运动神经元（Df）的胆碱能活性。将这些药物和乙酰胆碱应用于浴槽中，导致神经元膜的电导呈剂量依赖性变化以及相应的去极化。根据剂量-反应关系确定了药物的相对效力，其有效性的排序如下：卡巴胆碱远大于左旋咪唑大于噻嘧啶大于莫仑太尔。拮抗剂美加明消除了对所有这些药物的反应，从而获得了这些药物作用于同一作用位点的证据。得出的结论是，这些强效驱虫药的弱杀虫作用可能部分源于它们对昆虫神经元的弱胆碱能激动剂作用，这与它们对蠕虫神经和肌肉组织的乙酰胆碱受体的强效激动剂作用形成对比。在不同无脊椎动物组织上效力的显著差异似乎反映了昆虫和线虫之间乙酰胆碱受体特性的差异。为了促进合理设计对哺乳动物毒性低的广谱抗寄生虫药物，需要进一步表征无脊椎动物中的神经递质受体。
