Takahama Kazuo, Shirasaki Tetsuya
Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Cough. 2007 Jul 9;3:8. doi: 10.1186/1745-9974-3-8.
Narcotic antitussives such as codeine reveal the antitussive effect primarily via the mu-opioid receptor in the central nervous system (CNS). The kappa-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether delta-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic antitussives are the most potent antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO2 gas exposure, coughing is difficult to inhibit with centrally acting antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results.
可待因等麻醉性镇咳药主要通过中枢神经系统（CNS）中的μ-阿片受体发挥镇咳作用。κ-阿片受体似乎也在一定程度上有助于药物产生镇咳效果。关于δ-受体是否参与促进镇咳作用存在争议。外周阿片受体似乎具有某些有限的作用。尽管麻醉性镇咳药是目前最有效的镇咳药，但某些类型的咳嗽，如慢性咳嗽，即使使用可待因也特别难以抑制。在豚鼠中，由气管分叉处机械刺激引起的咳嗽不能被可待因抑制。在暴露于SO2气体引起亚急性支气管炎的豚鼠中，使用可待因等中枢性镇咳药很难抑制咳嗽。一些研究表明，神经激肽参与了对可待因耐药咳嗽的发生发展。然而，支持这一说法的证据仍然不足。在实验动物中表征阿片类药物耐药性咳嗽，并确定哪些实验诱导的咳嗽与人类的哪些类型咳嗽相对应非常重要。在这篇综述中，我们描述了麻醉性镇咳药的镇咳作用机制，探讨了对可待因敏感和耐药的咳嗽，并包括了我们自己的研究结果。
