Pharmacological Analysis of Positive Chrono- and Inotropic Responses to Denopamine (TA-064) in Dog Cross-Circulated Atrial and Ventricular Preparations

Positive chrono- and inotropic responses to denopamine (TA-064, (—)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol), a new and orally active cardiotonic agent, were investigated in the canine isolated right atrial or left ventricular preparation which was cross-circulated with blood from another support dog. Denopamine dose-dependently increased the sinus rate, right atrial and left ventricular contractile force. Denopamine was one to two orders of magnitude less potent than isoproterenol. The positive chrono- and inotropic effects of denopamine in isolated, blood-perfused right atria were dose-dependently inhibited by treatment with propranolol and atenolol. The effects of denopamine were only slightly attenuated by ICI 118,551 in doses which completely suppressed the positive chrono- and inotropic effects of procaterol. The increases in sinus rate and atrial contractility induced by denopamine were partially but significantly attenuated by treatment with imipramine in a dose which suppressed the effects of tyramine and potentiated the effects of norepinephrine. These results indicate that denopamine is a highly selective beta-1 adrenoceptor agonist in isolated, blood-perfused dog heart preparations, and they also suggest a mild catecholamine-releasing activity through tyramine-like action in isolated right atria.