Isoeugenolol : A Selective β_1-Adrenergic Antagonist With Tracheal and Vascular Smooth Muscle Relaxant Properties

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Abstract

Isoeugenolol (1.0, 3.0, 5.0 mg/kg, i.v.) produced a dose-dependent bradycardia and a decrease in blood pressure in anesthetized Wistar rats. Isoeugenolol inhibited the tachycardia effects induced by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by (-)phenylephrine. In isolated guinea pig tissues, isoeugenolol antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects on the atria and tracheal relaxations in a concentration-dependent manner. The apparent pA<SUB>2</SUB> values for isoeugenolol on right atria, left atria and trachea were 7.63±0.03, 7.89±0.12 and 6.12±0.05, respectively, indicating that isoeugenolol was a highly selective β<SUB>1</SUB>-adrenoceptor blocker. On the other hand, isoeugenolol produced a mild direct cardiac depression at high concentration and was without intrinsic sympathomimetic activity (ISA). In isolated rat thoracic aorta, isoeugenolol relaxed more potently the contractions induced by (-)phenylephrine (10 μM) and 5-HT (10 μM) than those by high K<SUP>+</SUP> (75 mM). In isolated guinea pig trachea, isoeugenolol attenuated the carbachol (1 μM)-contracted trachea more significantly than those contracted with high K<SUP>+</SUP>. Furthermore, the binding characteristics of isoeugenolol and various β-adrenoceptor antagonists were evaluated in [<SUP>3</SUP>H]CGP-12177 binding to rat ventricle, lung and interscapular brown adipose tissue (IBAT) membranes. The -log IC<SUB>50</SUB> values of isoeugenolol for predominate β<SUB>1</SUB>-, β<SUB>2</SUB>- and β<SUB>3</SUB>-adrenergic receptor sites were 5.82±0.09, 4.74±0.05 and 4.73±0.12, respectively. In conclusion, isoeugenolol was found to be a highly selective β<SUB>1</SUB>-adrenoceptor antagonist with tracheal and vascular smooth muscle relaxant activities, but was devoid of α-adrenoceptor-blocking action.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 80(2), 127-136, 1999-06-01

    The Japanese Pharmacological Society

References:  40

Codes

  • NII Article ID (NAID)
    10008194870
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4771930
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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