Young-Tso Lin (1), Bin-Nan Wu (2), Chiou-Fenq Horng (2), Yeun-Chih Huang
(2), Show-Jen Hong (2), Yi-Ching Lo (2), Chang-Jenq Cheng (2) and Ing-Jun
Chen (2,*)
Departments of (1) Cardiovascular Surgery and (2) Pharmacology, Kaohsiung
Medical College, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
(*) To whom correspondence should be addressed.
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 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 beta1-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 microM) and 5-HT
(10 microM) than those by high K+ (75 mM). In isolated guinea
pig trachea, isoeugenolol attenuated the carbachol (1 microM)-contracted
trachea more significantly than those contracted with high K+.
Furthermore, the binding characteristics of isoeugenolol and various beta-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 beta1-, beta2-
and beta3-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 beta1-adrenoceptor antagonist with tracheal
and vascular smooth muscle relaxant activities, but was devoid of alpha-adrenoceptor-blocking
action.
Keywords: Isoeugenol, beta1-Adrenoceptor antagonist, Smooth
muscle relaxation,
Interscapular brown adipose tissue, Radioligand binding study