Key result
TA-064 administered intraduodenally at 0.1 mg/kg increased cardiac contractile force by 120% of the control for over 150 minutes in animal models.
Why the study?
Does TA-064 improve cardiac contractile force in animal models?
Does TA-064 improve cardiac contractile force in animal models?
TA-064 is an orally active, selective positive inotropic agent with beta 1-adrenoceptor agonistic properties.
TA-064 shows positive inotropy in animal models; leaves open clinical translation and human trials.
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 beta 1-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 150 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 1-adrenoceptor agonistic property.
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Nagao et al. (1984) studied this question. TA-064 vs. isoproterenol, dobutamine, and control was evaluated on cardiac contractile force. TA-064 administered intraduodenally at 0.1 mg/kg increased cardiac contractile force by 120% of the control for over 150 minutes in animal models.
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