dinoprost and ibopamine

The effects of the novel inotropic pro-drug, ibopamine, and the de-esterified active form, epinine (N-methyldopamine), were investigated in isolated canine circumflex coronary arteries in vitro. Both ibopamine and epinine produced concentration-dependent contractions of isolated canine coronary arteries, with epinine being approximately 7-fold more potent than ibopamine. The coronary vasoconstrictor response produced by ibopamine was inhibited completely by the irreversible alpha-adrenoceptor antagonist, phenoxybenzamine, whereas the response produced by epinine was transformed into relaxation which was inhibited by the beta-adrenoceptor antagonist, propranolol. The results indicate that ibopamine has the capacity to produce coronary arterial vasoconstriction, but that this activity may be partially offset by the beta-adrenoceptor-mediated activity of the active form, epinine.

Topics: Animals; Cardiotonic Agents; Coronary Circulation; Deoxyepinephrine; Dinoprost; Dogs; Dopamine; In Vitro Techniques; Prodrugs

The pharmacological activity of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, was compared with that of epinine (N-methyldopamine) and dopamine on some isolated organs. The results of this study show that ibopamine and epinine exerts a positive inotropic effect on cat papillary muscle by stimulating the cardiac beta 1- and alpha-adrenoceptors; a positive chronotropic effect on cat right atrium by stimulating the cardiac beta 1-adrenoceptors; a relaxing effect on guinea-pig trachea by stimulating beta 2-adrenoceptors; a relaxing effect on rabbit splenic artery pretreated with phenoxybenzamine and contracted with PGF2 alpha by stimulating the DA1 receptors; an inhibitory effect on the vasoconstriction of rabbit ear artery induced by electrical stimuli by stimulating the DA2 receptors. Esterase activation, either by organ or plasma enzymes, appeared to be a prerequisite of ibopamine activity. Suppression of this activity by esterase inhibitors confirmed that the pharmacological responses are related to the formation of epinine. The magnitude and rate of response of some isolated organs to ibopamine appeared to be related to the esterase content of the tissue.

Topics: Animals; Cardiotonic Agents; Cats; Deoxyepinephrine; Dinoprost; Dopamine; Electric Stimulation; Female; Guinea Pigs; Heart; Hydrolysis; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Myocardial Contraction; Myocardium; Phenoxybenzamine; Prostaglandins F; Rabbits; Trachea