β-Adrenoceptor Profile of Ractopamine HCl in Isolated Smooth and Cardiac Muscle Tissues of Rat and Guinea-pig

Abstract

The investigational sympathomimetic amine, ractopamine hydrochloride, has been profiled for adrenergic activity in selected smooth and cardiac muscle preparations. There was no significant interaction of ractopamine with alpha-adrenergic receptors in the rat vas deferens at concentrations up to 10(-5) M. However, ractopamine produced a concentration-dependent increase in the force and rate of contractions of atria isolated from normal and reserpinized guinea-pigs (EC50 = 1 x 10(-7) M). These increases were submaximal compared with isoprenaline (70-85%), suggesting partial agonist activity at the beta 1-receptor site. Ractopamine completely relaxed the KCl-contracted guinea-pig trachea and rat costo-uterine smooth muscle to their resting tensions (EC50 = 3 x 10(-7) and 5.5 x 10(-8) M, respectively), indicative of full beta 2-agonist properties. Propranolol blocked the response of ractopamine in isolated tracheal and atrial tissues (pA2 = 7.70), demonstrating a beta-adrenergic mechanism of activity. Ractopamine also exhibited antagonism of the response of the guinea-pig trachea to the beta-agonist, isoprenaline. Relative to other beta-agonists, ractopamine was 100-fold more potent than the phenethanolamines, salbutamol and ritodrine, at the beta 1-adrenoceptor, and approximately 7- to 11-fold more potent than ritodrine, but only one-sixth to one-tenth as potent as salbutamol at the beta 2-adrenoceptor. Thus, ractopamine possesses significant beta 1- and beta 2-agonist properties. The submaximal stimulation of the force and rate of atrial contractions is indicative of a partial beta 1-agonist, while the maximal relaxation of the tracheal and costo-uterine smooth muscle is characteristic of a full beta 2-agonist.