Affiliation:
1. Faculté de Médecine Paris-Ouest, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France
Abstract
Abstract
The effects of molsidomine and its metabolite linsidomine were studied on the guinea-pig isolated trachea and on the human isolated bronchus. These effects were compared with those of nitrate derivatives (sodium nitroprusside, isosorbide dinitrate), theophylline, zardaverine and isoprenaline. Linsidomine exerted a relaxant effect similar to that of sodium nitroprusside on the two types of preparations precontracted with acetylcholine, histamine or potassium chloride. Molsidomine was about one-hundredth as potent as linsidomine, and less efficacious. The effects of the two substances were not modified by removal of the human bronchial epithelium. The concentration-response curves of linsidomine and sodium nitroprusside were significantly shifted to the right by methylene blue (3 × 10−5 m) but the effects of isoprenaline were unmodified. The effects of linsidomine and sodium nitroprusside were potentiated specifically by zaprinast (10−6-10−5 m), an inhibitor of type Ia or V phosphodiesterases, whereas the effects of isoprenaline were potentiated by zardaverine (10−9-10−8 m), an inhibitor of class III and IV phosphodiesterases. The effects of all three substances (linsidomine, isoprenaline and sodium nitroprusside) were potentiated equally by theophylline (10−5-10−4 m), a nonspecific inhibitor of phosphodiesterases. It is concluded that linsidomine is a potent relaxant of the smooth muscle of the guinea-pig isolated trachea and human isolated bronchus. In terms of potency and efficacy, its effect is much superior to that of the parent compound molsidomine. It is suggested that linsidomine acts, like nitrate derivatives, through the guanylate cyclase-cGMP system.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献