Comparative Positive Inotropic Effects of TA-064 (Denopamine), a New Cardiotonic Agent, and Isoproterenol and Ouabain on Guinea Pig Ventricular Muscles

Abstract

The effects of TA-064 (TA) on "fast" and "slow" response action potentials and contractile tensions were studied in isolated guinea pig papillary muscles, and the findings were compared with those of isoproterenol (ISP) and ouabain. The results are as follows: (a) TA produced a dose-dependent (10(-7)-10(-5) M) increase in developed tension, with no significant changes in the resting membrane potential (RMP), action potential duration (APD), and maximum rate of rise of action potential (Vmax). (b) The concentration required to increase the developed tension by threefold ("equivalent concentration") were 10(-6) M with both TA and ouabain, while that of ISP was 5 x 10(-8) M. (c) TA increased the maximum rate of rise, dP/dtmax, and the maximum rate of fall, dR/dtmax, of the developed tension to the same extent, unlike those of ISP and ouabain. (d) Positive inotropic effects of TA (10(-7)-10(-5) M) were not completely abolished by atenolol (3.8 x 10(-5) M), a specific beta 1 blocker, whereas those of ISP were completely abolished. (e) The increasing effects of "equivalent concentration" of TA (10(-6) M) on the Vmax of the slow response were less than those of ISP (5 x 10(-8) M). These results suggest that the positive inotropic effects of TA are mainly due to stimulation of beta 1 adrenoceptors, but that the mode of action of the drug differs in several respects from that of ISP or ouabain.