Isoeugenolol: A Selective β1-Adrenergic Antagonist With Tracheal and Vascular Smooth Muscle Relaxant Properties

[摘要] References(40)Cited-By(11)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 pA2 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 β1-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+ (75 mM). In isolated guinea pig trachea, isoeugenolol attenuated the carbachol (1 μM)-contracted trachea more significantly than those contracted with high K+. Furthermore, the binding characteristics of isoeugenolol and various β-adrenoceptor antagonists were evaluated in [3H]CGP-12177 binding to rat ventricle, lung and interscapular brown adipose tissue (IBAT) membranes. The -log IC50 values of isoeugenolol for predominate β1-, β2- and β3-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 β1-adrenoceptor antagonist with tracheal and vascular smooth muscle relaxant activities, but was devoid of α-adrenoceptor-blocking action.

[学科分类] 药理学

[关键词] Isoeugenol;β1-Adrenoceptor antagonist;Smooth muscle relaxation;Interscapular brown adipose tissue;Radioligand binding study