Curtis M J
Department of Pharmacology, King's College London, United Kingdom.
J Neural Transm Suppl. 1990;31:17-38.
Why are calcium antagonists not used clinically in myocardial protection to prevent sudden death despite evidence from animal experiments that such activity may exist? The reason is that calcium antagonists are relatively vascular-selective and, at the sub-vasodilatory doses which have been tested clinically, do not inhibit the slow inward current in the myocardium. As a result a belief has grown in the fallacious concept that calcium antagonist activity in the myocardium is not a protective mechanism. Animal studies suggest that the opposite is the case. In my view, in the 20 years since the cardioprotective actions of verapamil were first demonstrated, an opportunity for drug development has been wasted. To rectify this, new drug development should begin with the objective of designing calcium antagonists with inbuilt site-selectivity for ischaemic tissue.
尽管动物实验表明钙拮抗剂可能具有心肌保护作用以预防猝死，但为何临床上未将其用于心肌保护呢？原因在于钙拮抗剂具有相对的血管选择性，并且在临床测试的亚血管扩张剂量下，不会抑制心肌中的缓慢内向电流。结果，一种错误观念逐渐形成，即认为钙拮抗剂在心肌中的活性不是一种保护机制。动物研究表明事实恰恰相反。在我看来，自维拉帕米的心脏保护作用首次被证实的20年来，药物研发的一个机会被浪费了。为纠正这一点，新药研发应以设计对缺血组织具有内在位点选择性的钙拮抗剂为目标展开。
