STUDIES OF COLISTIN SALTS AND ITS DERIVATIVES, METHANESULFONATE ON THE CIRCULATORY SYSTEM

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  • YAMADA SHIGEO
    Department of Pharmacology, School of Pharmaceutical Sciences, Showa University
  • MAYAHARA TAKATO
    Department of Pharmacology, School of Pharmaceutical Sciences, Showa University
  • MATSUMOTO TOMONORI
    Section of Pharmacology, Kayaku Antibiotics Research Co., Ltd.
  • MATSUO SHOICHI
    Section of Pharmacology, Kayaku Antibiotics Research Co., Ltd.
  • KAMIJO KAZUYA
    Department of Pharmacology, School of Medicine, Showa University

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Other Title
  • 循環器系に対するコリスチン塩類およびその誘導体メタンスルホン酸の作用
  • ジュンカンキケイ ニ タイスル コリスチン エンルイ オヨビ ソノ ユウドウタイ メタンスルホンサン ノ サヨウ

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Abstract

Comparative observations were made on the acnte toxicity and effects on the circulatory system and smooth muscle caused by colistin salts such as colistin sulfate (C-S), colistin tartrate (C-T), colistin pantothenate (C-P) and other colistin derivatives such as sodium methanesulfonate (C-M).<BR>The following results were obtained.<BR>1. The LD50 in mice was 9.1mg/kg and 21.5mg/kg for C-S; 71.5, 11.5mg/kg and 43.0mg/kg for C-T; 15.7 and 75.0mg/kg for C-P; and 740 and 510mg/kg for C-M by intravenous and intraperitoneal injection, respectively.<BR>2. On isolated cardiac muscle, all three colistin salts act facilitatively, while C-M acted paralytically.<BR>The mechanisms of action were an excitation on the peripheral sympathetic nerve for the salts and a direct paralytic action on myocardium for C-M. The intensity of action by the salts was according to the order C-S>C-T>C-P.<BR>3. Colistin salts exerted a contractile action on peripheral blood vessels and C-M dilatatory action.The intensity of the salts action followed the order C-S>C-T>C-P.<BR>4. Colistin salts decreased on the isolated rabbit's intestinal movement and the mechanism of action was probably due to the cxcitation at the peripheral sympathetic nerve. C-M exerted a paralytic action on intestinal movement, probably directly on the smooth muscle in the intestinal wall. The intensity of action followed the order C-S>C-T>C-P.<BR>5. Colistin salts and C-M exerted anti-histamine, anti-acetylcholine and anti-barium action. C-S was most intense, followed by C-T, then C-P, with C-M the least active.

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