Beta-adrenoceptor profile of ractopamine HCl in isolated smooth and cardiac muscle tissues of rat and guinea-pig.
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.
Toxicology Division, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, Indiana 46140.
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012312:Ritodrine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D010627:Phenethylamines; D011943:Receptors, Adrenergic, beta; C060897:ractopamine; D011433:Propranolol; D012312:Ritodrine; D007545:Isoproterenol; D000420:Albuterol