Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole
Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole
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DOI：
10.1017/s0031182005008668
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发表时间：
2005-01-01
期刊：
影响因子：
2.4
通讯作者：
Robertson, AP
中科院分区：
文献类型：
--
作者：
Martin, RJ;Verma, S;Robertson, AP
在此，我们回顾了胆碱能驱虫药（左旋咪唑、噻嘧啶等）作用方式的最新研究。我们还包括对自由生活的线虫秀丽隐杆线虫的研究材料。这些药物作用于单一受体群的最初想法虽然很有吸引力，但已被证明过于简单化。自由生活线虫和寄生线虫的体细胞肌肉组织上都有多种类型的烟碱乙酰胆碱受体（nAChR）。每种类型都有不同的（有时是微妙的）药理学特性。这些发现的意义在于：（1）优先激活多种 nAChR 类型的驱虫药组合预计会更有效； (2) 对于一种亚型已消失的耐药寄生虫分离株，其他胆碱能驱虫药可能仍然有效。 nAChR 不仅有多种类型，而且最近的研究表明这些受体可以被调节；通过改变受体特性（例如磷酸化状态）可以增加寄生虫对固定浓度药物的反应。这些发现为提高现有化合物的功效提供了一种潜在的方法，可以替代昂贵且耗时的新型驱虫剂的开发。
Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types Would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there Multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.