Cardiovascular effects of a new positive inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-((3,4-dimethoxyphenethyl)amino)-ethanol (TA-064) in the anesthetized dog and isolated guinea pig heart.

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The positive inotropic effect of TA-064, (-) - (R) -1- (p-hydroxyphenyl) -2- [(3, 4-dimethoxyphenethyl) amino] ethanol, was studied in the anesthetized dog and isolated guinea pig heart. An intravenous administration of TA-064 dose-dependently increased the cardiac contractile force with little effect on blood pressure in dogs. The positive inotropic activity of TA-064 was 1/100 that of isoproterenol and similar to that of dobutamine. This effect of TA-064 was stereospecific, and it was blocked by practolol. Thus TA-064 has beta1 -adrenoceptor agonistic action. The positive inotropic effect of TA-064 was more pronounced than the positive chronotropic effect, compared with those of isoproterenol. Similar effect of TA-064 was observed in the reserpinized dog and in the isolated perfused heart of the guinea pig as well. TA-064 administered intraduodenally at a dose of 0.1 mg/kg increased contractile force by 120% of the control, and the effect lasted for more than 160 min. TA-064 given in the femoral artery demonstrated a very weak vasodilating effect on the artery. TA-064 is an orally active, positive inotropic agent. The selective positive inotropic action of TA-064 may result from its beta<SUB>1</SUB> -adrenoceptor agonistic property.
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