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Eugenodilol: a third-generation beta-adrenoceptor blocker, derived from eugenol, with alpha-adrenoceptor blocking and beta2-adrenoceptor agonist-associated vasorelaxant activities.
- Source :
-
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 1999 Jul; Vol. 34 (1), pp. 10-20. - Publication Year :
- 1999
-
Abstract
- Eugenodilol, derived from natural eugenol, was first investigated with in vivo and in vitro models. In our in vivo study, eugenodilol (0.5, 1.0, and 1.5 mg/kg, i.v.) produced dose-dependent hypotensive and bradycardic responses in pentobarbital-anesthetized Wistar rats. Eugenodilol also inhibited the tachycardia and arterial pressor effects induced by (-)isoproterenol and phenylephrine, respectively. In our in vitro study, eugenodilol competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects and tracheal-relaxation responses on isolated guinea pig tissues in a concentration-dependent manner. The apparent pA2 values were 7.88+/-0.12 for right atria, 7.52+/-0.05 for left atria, and 7.33+/-0.15 for trachea, indicating that eugenodilol was a nonselective beta-adrenoceptor blocker. In thoracic aorta experiments, the apparent pA2 values of alpha-adrenoceptor blockade were 7.05+/-0.25 and 6.87+/-0.08 for eugenodilol and labetalol, respectively. In addition, eugenodilol produced cumulative relaxation responses on isolated guinea pig tracheal strips. The effects were competitively antagonized by ICI 118,551 (10(-8)-10(-6) M), a relatively selective beta2-adrenoceptor antagonist. In the radioligand-binding assay, the Ki values of [3H]CGP-12177 binding to rat ventricle and lung membranes were 9.72 and 48.29 nM, respectively, and the value of [3H]prazosin binding to rat brain membrane was 38.72 nM. These results further confirmed the alpha/beta-adrenoceptors-blocking activities of eugenodilol reported in the functional studies. We conclude that eugenodilol is a novel third-generation beta-adrenoceptor blocker with ancillary blocking activity at alpha-adrenoceptors and weak sympathomimetic activity at beta2-adrenoceptors.
- Subjects :
- Anesthesia
Animals
Aorta, Thoracic drug effects
Bradycardia chemically induced
Dose-Response Relationship, Drug
Drug Interactions
Eugenol pharmacology
Female
Guinea Pigs
Hypotension chemically induced
In Vitro Techniques
Isoproterenol pharmacology
Labetalol pharmacology
Male
Phenylephrine pharmacology
Radioligand Assay
Rats
Rats, Wistar
Time Factors
Trachea drug effects
Adrenergic beta-Agonists pharmacology
Adrenergic beta-Antagonists pharmacology
Eugenol analogs & derivatives
Muscle Contraction drug effects
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0160-2446
- Volume :
- 34
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10413061
- Full Text :
- https://doi.org/10.1097/00005344-199907000-00003