New Inotropic Agents for Treatment of Heart Failure
New positive inotropic agents have been synthesized and they are under intensive research to examine whether they are different from older drugs like digitalis and catecholamines in their mechanisms of action and in their clinical effectiveness. Among the positive inotropic agents, those developed by Japanese pharmaceutical laboratories were reviewed mainly in terms of their possible mechanism of action in the cardiac cells. OPC-8212 is orally active and has no chronotropic effect, which may prove beneficial in the treatment of heart failure. It increases intracellular cAMP by PDE inhibition, increases Ca current, and prolongs the duration of action potentials. OPC-8490, with a similar mechanism of action, has vasodilator and positive chronotropic action. MCI-154 is an orally active positive inotropic agent with vasodilator action. The mechanism of action also involves an increase in cAMP, but in addition, sensitization of the contractile elements to Ca has been demonstrated to play a partial role in the inotropic effect. RS-1893, ZSY-27, ZSY-39 and FK664 are orally active positive inotropic agents for which cAMP mechanisms are postulated, but their effectiveness was demonstrated only in experimentally produced heart failure.
KeywordsInotropic Agent Positive Inotropic Effect Heart Failure Model Positive Inotropic Agent Positive Chronotropic Effect
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