Calcium antagonists and coronary artery disease: an opportunity missed?
Calcium antagonists and coronary artery disease: an opportunity missed?
复制标题
钙拮抗剂和冠状动脉疾病：错失良机？
DOI：
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
M. Curtis
中科院分区：
文献类型：
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作者：
M. Curtis
尽管动物实验证据表明可能存在钙拮抗剂的作用，但为什么临床上不使用钙拮抗剂来保护心肌以防止猝死？原因是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舒张剂量下，不会抑制心肌中缓慢的内向电流。因此，人们越来越相信心肌中的钙拮抗剂活性不是一种保护机制的错误概念。动物研究表明情况恰恰相反。在我看来，自从维拉帕米的心脏保护作用首次被证明以来的20年里，药物开发的机会已经被浪费了。为了纠正这个问题，新药开发的目标应该是设计对缺血组织具有内在位点选择性的钙拮抗剂。
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.