Isoeugenolol: A selective beta(1)-adrenergic antagonist with tracheal and vascular smooth muscle relaxant properties

Isoeugenolol (1.0, 3.0, 5.0 mg/kg,i.v.) produced a dose-dependent bradycard ia and a decrease in blood pressure in anesthetized Wistar rats. Isoeugenol ol inhibited the tachycardia effects induced by (-)isoproterenol, but had n o blocking effect on the arterial presser responses induced by (-)phenyleph rine. In isolated guinea pig tissues, isoeugenolol antagonized (-)isoproter enol-induced positive inotropic and chronotropic effects on the atria and t racheal relaxations in a concentration-dependent manner. The apparent pA(2) 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 isoeugeno lol was a highly selective beta(1)-adrenoceptor blocker. On the other hand, isoeugenolol produced a mild direct cardiac depression at high concentrati on and was without intrinsic sympathomimetic activity (ISA). In isolated ra t thoracic aorta, isoeugenolol relaxed more potently the contractions induc ed by (-)phenylephrine (10 mu M) and 5-HT (10 mu M) than those by high K+ ( 75 mM). In isolated guinea pig trachea, isoeugenolol attenuated the carbach ol (1 mu M)-contracted trachea more significantly than those contracted wit h high Kf. Furthermore, the binding characteristics of isoeugenolol and var ious B-adrenoceptor antagonists were evaluated in [H-3]CGP-12177 binding to rat ventricle, lung and interscapular brown adipose tissue (IBAT) membrane s. The -log IC50 values of isoeugenolol for predominate beta(1)-, beta(2)- and beta(3)-adrenergic receptor sites were 5.82+/-0.09, 4.74+/-0.05 and 4.7 3+/-0.12, respectively. In conclusion, isoeugenolol was found to be a highl y selective beta(1)-adrenoceptor antagonist with tracheal and vascular smoo th muscle relaxant activities, but was devoid of alpha-adrenoceptor-blockin g action.