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

机译：Ca〜（2+）敏感剂的机制和药理学分类

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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.
机译：自20世纪80年代初以来，已经积累了广泛的努力，用于替代Digitalis和儿茶酚胺的新型羊皮蛋白，其正颞亢进（馅饼）与严重的不良反应有关，包括由于诱导心律失常和细胞损伤CA〜（2+）过载。已经为慢性充血性心力衰竭（CHF）患者的长期治疗而开发了几种新型的乱蓬蓬的转化剂，但目前没有一个新的CA〜（2+）流动者已经成功地表达了长期的明确改善慢性CHF患者的预后。具有Ca〜（2+）敏化作用的某些新型剂已被证明比实验动物的CHF模型中的CHF模型中的CA〜（2+）流动剂更有益，这表明新颖的发展Ca〜（2+）用于治疗心脏泵功能障碍的敏化剂可以提供慢性CHF患者的药理学治疗的突破。在新型Ca〜（2+）敏化剂的发展的基本药理学的早期阶段，经典的毒蕈碱受体激动剂卡巴醇可以用作分解新型CA〜（2+）敏感剂的作用方式的药理学工具治疗慢性CHF患者的潜力。

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