Cardiovascular effects of 2-amino-N-(2,6-dimethylphenyl)-N-(3-(3-pyridyl)propyl)propionamide dihydrochloride(Ro 22-9194) in the isolated, cross-perfused atrium of the dog.

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The cardiovascular effects of 2-amino-N-(2, 6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide dihydrochloride (Ro 22-9194) were investigated in the canine isolated atrial preparation perfused with arterial blood from another donor dog. Intravenous administration of Ro 22-9194 (0.3-3mg/kg) reduced heart rate and systemic arterial blood pressure of the donor dog. Simultaneously, in the isolated atrium perfused with donor's blood, negative chronotropic and inotropic responses were induced in a dose-dependent manner. Direct administration of Ro 22-9194 (1-300μg) into the sinus node artery of the isolated atrium induced negative chrono- and inotropic responses and a transient increase in coronary blood flow in a dose-related manner. Mexiletine (1-300μg) also induced negative chrono- and inotropic responses. The potency of Ro 22-9194 for negative cardiac effects was similar to that of mexiletine. The negative cardiac effects of Ro 22-9194 were not modified by atropine in doses which significantly inhibited the cardiac effects of acetylcholine. Ro 22-9194 did not affect the cardiac responses to norepinephrine and to acetylcholine significantly. These results suggest that Ro 22-9194 has non-cholinergic cardiac depressant properties with its vasodilating action, and it has neither anti-adrenergic nor anti-cholinergic actions on the dog heart.