In Vitro Characterization of the Effects of MCI-154, a Novel Cardiotonic Agent, on Cardiac Tissues

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In vitro cardiac effects of a cardiotonic drug, MCI-154, for which the main action mechanism was proposed to be the enhancement of Ca²⁺ sensitivity of cardiac contractile proteins, were investigated. MCI-154 (3×10^-8-3×10^-4 M) increased the developed tension in isolated ventricular muscles from cats, dogs, guinea pigs and rats and increased that of isolated left atrial muscles of guinea pigs and rats. However, species differences were observed in the responses to MCI-154. The positive inotropic potency of MCI-154 was stronger than those of amrinone and milrinone. In the isolated right atria from guinea pigs and rats, properties of the chronotropic effect of MCI-154 were different from those of amrinone and milrinone. The positive inotropic action of MCI-154 was not affected by phentolamine, propranolol, cimetidine and tetrodotoxin. MCI-154 did not inhibit cardiac Na⁺, K⁺-ATPase. MCI-154 modelately stimulated Ca²⁺-uptake of isolated cardiac sarcoplasmic reticulum (SR), but induced no release of Ca²⁺ the SR. These results support the view that the main mechanism for the action of MCI-154 is the enhancement of Ca²⁺ sensitivity of cardiac contractile proteins.