Effect of SMP-300, a New Na^+/H^+ Exchange Inhibitor, on Myocardial Ischemia and Experimental Angina Models in Rats

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We evaluated the effects of SMP−300(N−(aminoiminomethyl)−11−chloro−5, 6, 7, 8−tetrahydro−8−oxo−4H−pyrrolo[3, 2, 1−kl][1]benzazocine−2−carboxamide monomethanesulfonate monohydrate), a newly synthesized compound, on Na<SUP>+</SUP>/H<SUP>+</SUP> exchange activity in rat cardiomyocytes and on other ion transporters, channels and receptors.We also investigated the protective effects of SMP−300 in isolated ischemic rat hearts and rat isoproterenol− or vasopressin−induced experimental angina models.SMP−300 concentration−dependently inhibited recovery from acidosis in rat myocytes, and its IC<SUB>50</SUB> for Na<SUP>+</SUP>/H<SUP>+</SUP> exchange was 6 nM.In comparison, its IC<SUB>50</SUB>s for Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchange and for the Na<SUP>+</SUP> channel were >1000 nM, and those for other channels or receptors tested were >10, 000 nM.In rat isolated perfused hearts, SMP−300(10<SUP>-8</SUP>−10<SUP>-7</SUP>M), administered only at preischemia and not during reperfusion, significantly improved the postischemic recovery of cardiac function.SMP−300(0.03−0.3 mg/kg, i.v.)or 5−(N−ethyl−N−isopropyl)−amiloride(1 mg/kg, i.v.)prevented the isoproterenol−induced ST−segment depression in the ECG of anesthetized rats, in a dose−dependent manner.SMP−300(0.1 mg/kg, i.v.)and 5−(N−ethyl−N−isopropyl)−amiloride(1 mg/kg, i.v.)also inhibited the vasopressin−induced ST−segment depression in the ECG of anesthetized rats.This is the first report presenting the protective effect of Na<SUP>+</SUP>/H<SUP>+</SUP> exchange inhibitors on isoproterenol− or vasopressin−induced ECG changes in rats, providing the future perspective of SMP−300, a potent Na<SUP>+</SUP>/H<SUP>+</SUP> exchange inhibitor, as an anti−anginal drug.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 84(2), 196-205, 2000-10-01

    公益社団法人 日本薬理学会

参考文献:  38件中 1-38件 を表示

被引用文献:  2件中 1-2件 を表示

各種コード

  • NII論文ID(NAID)
    10008185775
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5549388
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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