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化学刺激诱发咳嗽样反射的药理学研究(作者译)

[Pharmacological studies on the cough-like reflex induced by chemical stimulation (author's transl)].

作者信息

Yanaura S, Nishimura T, Hosokawa T, Abe Y, Iwase H

出版信息

Nihon Yakurigaku Zasshi. 1978 Apr;74(3):345-52. doi: 10.1254/fpj.74.345.

Abstract

To investigate the mechanism of the cough-like reflex (CLR), we employed 1.1-dimethyl-4-phenylpiperazinium iodide (DMPP). In dogs anesthetized with alpha-chloralose, CLR was induced by administration of DMPP (i.v. and intracarotid arterial), lobeline and nicotine. Repeated administration of DMPP did not cause a tachphylaxis, however, lobeline and nicotine did induce a tachphylaxis. DMPP (i.a.), lobeline, nicotine and histamine caused an increase in respiratory resistance as measured by a Respiratory Resistance Meter, while DMPP (i.v.) did not. The ED50 of morphine, codeine, oxymethebanol, picoperidamine and piclobetol on CLR with DMPP was higher than that of those drugs employed for the peripherally-induced cough. CLR with DMPP was not affected by isoproterenol, ephedrine, atropine and propranolol. CLR was markedly depressed by hexamethonium and slightly depressed by benzonate. CLR was abolished after bilateral vagotomy or bilateral denervation of the carotid sinus nerves. These results indicate that the mechanism of CLR with DMPP is different from that of peripherally-induced cough and the carotid body chemoreceptor plays an important role in CLR with DMPP. This CLR may be useful for demonstrating the site of action and the mechanism of antitussive drugs.

摘要

为研究咳嗽样反射(CLR)的机制,我们使用了1,1 - 二甲基 - 4 - 苯基哌嗪碘化物(DMPP)。在用α - 氯醛糖麻醉的犬中,通过静脉注射和颈动脉内注射DMPP、洛贝林和尼古丁诱导CLR。重复注射DMPP未引起快速耐受,然而,洛贝林和尼古丁确实诱导了快速耐受。通过呼吸阻力计测量,DMPP(动脉内注射)、洛贝林、尼古丁和组胺可导致呼吸阻力增加,而DMPP(静脉注射)则不会。吗啡、可待因、羟甲左吗南、匹哌立登和匹氯贝特对DMPP诱导的CLR的半数有效量(ED50)高于那些用于外周诱导咳嗽的药物。DMPP诱导的CLR不受异丙肾上腺素、麻黄碱、阿托品和普萘洛尔的影响。六甲铵可显著抑制CLR,苯佐那酯可轻度抑制CLR。双侧迷走神经切断术或双侧颈动脉窦神经去神经支配后,CLR消失。这些结果表明,DMPP诱导的CLR机制与外周诱导咳嗽的机制不同,并且颈动脉体化学感受器在DMPP诱导的CLR中起重要作用。这种CLR可能有助于证明镇咳药物的作用部位和机制。

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