Freedman D D, Waters D D
Montréal Heart Institute.
Drugs. 1987 Nov;34(5):578-98. doi: 10.2165/00003495-198734050-00005.
The newer dihydropyridine calcium antagonists are structurally related to nifedipine, but may provide greater vascular selectivity and wider clinical utility. Five new dihydropyridines-nisoldipine, nicardipine, nimodipine, felodipine and nitrendipine-are reviewed with regard to their preclinical pharmacology, haemodynamic effects and clinical indications. Nisoldipine is a potent arterial vasodilator with minimal electrophysiological and negative inotropic effects. Although data are still preliminary, the drug has shown some efficacy in both exertional angina and essential hypertension. The dosing interval is not yet clearly established, but may be twice daily. Utility in congestive heart failure awaits confirmation, but preliminary studies are promising. Nicardipine is an especially potent peripheral, cerebral and coronary arterial vasodilator that causes 10-fold less myocardial depression in animals than nifedipine, and may provide important cardioprotective effects during ischaemia. Human haemodynamic studies have confirmed nicardipine's lack of negative inotropism, its ability to reduce coronary and peripheral vascular resistance, and its lack of effect on cardiac conduction. Several controlled trials have documented its efficacy in exertional angina, vasospastic angina, and essential hypertension. Nicardipine's potential as an antiatherosclerotic agent is currently under investigation. Nimodipine is undergoing a unique clinical development programme aimed at cerebrovascular disorders. In almost all species, nimodipine selectively increases cerebral blood flow and reverses cerebral artery spasm without altering cerebral oxidative metabolism or systemic blood pressure. In humans, a large, double-blind, placebo-controlled trial in subarachnoid haemorrhage showed that nimodipine significantly reduced the severity of neurological deficits associated with delayed cerebral vasospasm. Several uncontrolled trials with larger numbers of patients support these results. Nimodipine has also proved useful in reducing cerebral artery spasm during intracranial surgery, and in the prophylactic treatment of migraine headaches. A preliminary study of nimodipine in acute stroke showed promising results in limiting neurological disability. Felodipine is a very potent systemic arterial vasodilator with negligible myocardial depressant activity. It is also a renal artery vasodilator. Unlike the other new dihydropyridines, felodipine prolongs the A-H interval on electrophysiological testing, but only to about 50% of that observed with verapamil. Felodipine is undergoing clinical trials in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
新型二氢吡啶类钙拮抗剂在结构上与硝苯地平相关，但可能具有更高的血管选择性和更广泛的临床应用价值。本文综述了五种新型二氢吡啶类药物——尼索地平、尼卡地平、尼莫地平、非洛地平和尼群地平——的临床前药理学、血流动力学效应及临床适应证。尼索地平是一种强效的动脉血管扩张剂，对电生理及负性肌力作用极小。尽管数据仍属初步，但该药在劳力性心绞痛和原发性高血压方面均显示出一定疗效。给药间隔尚未明确确定，但可能为每日两次。其在充血性心力衰竭中的应用有待证实，但初步研究结果令人鼓舞。尼卡地平是一种特别强效的外周、脑及冠状动脉血管扩张剂，在动物实验中，其导致的心肌抑制作用比硝苯地平小10倍，且在缺血期间可能具有重要的心脏保护作用。人体血流动力学研究证实，尼卡地平无负性肌力作用，能够降低冠状动脉及外周血管阻力，且对心脏传导无影响。多项对照试验已证明其在劳力性心绞痛、血管痉挛性心绞痛及原发性高血压方面的疗效。尼卡地平作为抗动脉粥样硬化药物的潜力目前正在研究中。尼莫地平正在进行一项针对脑血管疾病的独特临床研发项目。在几乎所有物种中，尼莫地平可选择性增加脑血流量并逆转脑动脉痉挛，而不改变脑氧化代谢或全身血压。在人类中，一项针对蛛网膜下腔出血的大型双盲安慰剂对照试验表明，尼莫地平可显著降低与迟发性脑血管痉挛相关的神经功能缺损的严重程度。多项纳入更多患者的非对照试验支持了这些结果。尼莫地平在减少颅内手术期间的脑动脉痉挛以及偏头痛的预防性治疗方面也已证明有效。一项关于尼莫地平治疗急性中风的初步研究显示，在限制神经功能障碍方面取得了令人鼓舞的结果。非洛地平是一种非常强效的全身动脉血管扩张剂，心肌抑制活性可忽略不计。它也是一种肾动脉血管扩张剂。与其他新型二氢吡啶类药物不同，非洛地平在电生理测试中可延长A-H间期，但仅为维拉帕米所观察到的约50%。非洛地平正在进行原发性高血压的临床试验。（摘要截取自400词）
