Mechanisms and Pharmacological Classification of Ca~(2+) Sensitizers

摘要

Since early 1980's, an extensive effort has been accumulated for the development of novel cardiotonic agents to replace digitalis and catecholamines, the positive inotropic effect (PIE) of which are associated with serious adverse effects, including the induction of arrhythmias and cell injury due to the Ca~(2+) overload. Several novel cardiotonic agents have been developed for the long-term treatment of the patients with chronic congestive heart failure (CHF), but currently none of the novel Ca~(2-) mobilizers have succeeded in showing the definite improvement of the long-term prognosis in the chronic CHF patients. Certain novel agents with Ca~(2+) sensitizing action have been shown to be more beneficial than Ca~(2+) mobilizers in CHF models of experimental animals and small and/or middle scale clinical trials, which indicates that the development of novel Ca~(2+) sensitizers for the treatment of the cardiac pump dysfunction could provide a breakthrough of the pharmacological therapy of the chronic CHF patients. In the early stage of the basic pharmacology for the development of novel Ca~(2+) sensitizers, the classic muscarinic receptor agonist carbachol could be used as the pharmacological tool to differentiate the mode of action of novel Ca~(2+) sensitizers having potential for the treatment of the chronic CHF patients.