STRUCTURE AND ACTIVITY IN TETRODOTOXIN DERIVATIVES

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  • 出口 健彦
    Medical Laboratory for Pharmacology, Central Research Laboratories, Sankyo Co.

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Tetrodotoxin known as a powerful neurotoxin blocks electrical excitation of nerve and muscle cell membranes at very low concentrations (1, 2). The mechanism of its action is shown to be specific blockage of sodium conductance increase in excitation of membranes leaving delayed increase in potassium conductance almost intact (2-6). This specificity and intensity in action has attracted attention of physiologists and pharmacologists in the world, and many investigators are now utilizing the toxin as an interesting pharmacological tool (e.g. 7-14). This toxin has varieties of pharmacological effects in both conscious and anesthetized animals, e.g., blood pressure reduction, respiratory depression, nausea and vomiting, motor disorder, loss of various sensations (cf. 13). The respiratory failure is believed to cause death in animals received given high dosages. Recently, chemical structures of tetrodotoxin and related substances were clarified by great efforts of researchers in Japan and the United States using the advanced physical techniques in the field of natural products chemistry (15-18). It is of interest to investigate the pharmacological properties of the compounds structurally related to tetrodotoxin in view of the powerful and specific action of tetrodotoxin on membrane excitation and its relation to the unique structure. The author wishes to present here observations upon some of the pharmacological properties of nine related compounds and discussions on the structure-activity relationship in tetrodotoxin.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 17 (2), 267-278, 1967

    公益社団法人 日本薬理学会

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