Non-relaxant properties of neuromuscular blocking drugs.
Non-relaxant properties of neuromuscular blocking drugs.
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神经肌肉阻滞药物的非松弛特性。
DOI：
10.1093/bja/54.2.147
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发表时间：
1982
影响因子：
9.8
通讯作者：
W. Bowman
中科院分区：
文献类型：
--
作者：
W. Bowman
理论上，具有神经肌肉阻断活性的新化合物还可能产生几乎任何类型的不良药理作用。然而，与任何其他类别的药物相比，该领域对结构-作用关系的积累的知识使得药物化学家能够更可预测地生产有效的神经肌肉阻断药物，并且更少依赖偶然性（参见，例如，Martin-Smith，1971）。因此，通过适当的分子设计可以完全避免大多数类型的不需要的活性，并且任何确实产生不寻常的不需要的作用的新化合物通常可以在临床前测试的早期阶段被丢弃。正如经验所告诉的，神经肌肉阻滞药物的额外和不良作用主要（尽管可能不完全）源于分子的两个特征，正如 Paton（1959）在 20 多年前指出的那样。一个特征是一般使用的药物都是有机碱，因此它们有时可能会产生由此类化合物产生的相当非特异性的作用（例如组胺释放）。另一个是，为了与神经肌肉接头处胆碱受体的识别位点相互作用（即达到其预期效果），药物必须与乙酰胆碱具有某种化学关系。因此，它们有可能在其他位点（例如胆碱酯酶、烟碱型自主神经节受体和毒蕈碱受体）与乙酰胆碱竞争或模仿乙酰胆碱。 Marshall (1980) 最近回顾了非去极化神经肌肉阻滞药物对胆碱感受器而非运动终板的作用。在下面的描述中，讨论了由这两个主要分子特征引起的作用。一些目前还不能采取的额外行动
Theoretically, new compounds with neuromuscular blocking activity might additionally produce almost any type of unwanted pharmacological effect. However, the accumulated knowledge of structure-action relationships in this field is such that medicinal chemists are able to produce effective neuromuscular blocking drugs more predictably, and with less reliance on serendipity, than is the case with any other class of drugs (see, for example, Martin-Smith, 1971). Consequently, most kinds of unwanted activity can be avoided altogether by appropriate molecular design, and any new compounds that do happen to produce unusual unwanted effects can often be discarded at an early stage in preclinical tests. The result is, as experience has taught, that the additional and unwanted actions of neuromuscular blocking drugs mainly (although perhaps not entirely) stem from two characteristic features of the molecules, as pointed out by Paton (1959) more than 20 years ago. One characteristic feature is that the drugs in general use are all organic bases and they might therefore give rise to the rather non-specific effects sometimes produced by such compounds (eg histamine release). The other is that, in order to interact with the recognition sites of the cholinoceptors at the neuromuscular junction (ie to achieve their desired effect), the drugs must bear some chemical relationship to acetylcholine. Consequently, there is the possibility that they might compete with or mimic acetylcholine at other sites (eg cholinesterase, nicotinic autonomic ganglion receptors, and muscarinic receptors). Marshall (1980) has recently reviewed the actions of nondepolarizing neuromuscular blocking drugs at cholinoceptors other than those at the motor endplate. In the following description actions arising from these two main molecular features are discussed. A few additional actions that as yet cannot