具有独特双重作用机制的抗心绞痛新药:尼可地尔

A new class of antianginal drug with dual mechanism of action:Nicorandil

尼可地尔是日本研制的新一类抗心绞痛药物,具有双重抗心绞痛机制:硝酸酯类作用扩张静脉和心外膜冠状动脉,以及开放K+-ATP通道引起外周动脉和冠状动脉阻力血管扩张。其药理作用降低心脏前后负荷,增加冠状动脉血流,改善冠状循环,并防止冠状动脉痉挛。基于对线粒体的ATP敏感的钾通道的作用,尼可地尔发挥药物性预适应作用以及缺血或再灌注导致的心肌损伤的心脏保护作用。日本、欧洲和中国的临床报告提示尼可地尔具有与硝酸酯、β受体阻滞药和钙拮抗药相当的抗心绞痛作用。临床试验显示尼可地尔可预防稳定型心绞痛患者心绞痛发作及改善运动耐力。IONA和JCAD研究显示稳定型心绞痛患者长期服用尼可地尔可显著改善预后,减少主要冠状动脉事件或心血管死亡。尼可地尔耐受性好,无耐药性,不良反应轻微,如头痛、恶心、脸红和头晕。有报告尼可地尔可引起口腔、肛门及胃肠道溃疡。故尼可地尔是耐受良好的抗心绞痛新药,有血管扩张和心脏保护作用。其临床作用与当前的抗心绞痛药物不同,当其他药物控制心绞痛不满意时可加用尼可地尔。

Nicorandil is a new class of antianginal drug which was developed originally in Japan. The antianginal effects of nicorandil are demonstrated by its dual mechanism of action.The nitrate-like action induces dilatation of systemic venous and epicardial coronary arteries, and the KATP channel opening action induces dilatation of peripheral arteries and coronary arterial resistant vessels. These pharmacological mechanisms decrease preload and afterload, and improve coronary circulation via increasing coronary blood flow and the prevention of vasospasms. Nicorandil has been reported to have pharmacological preconditioning and cardioprotective effects against myocardial injury induced by ischemia and reperfusion through activation of mitochondrial ATP sensitive potassium cannels. Clinical reports from Japan, Europe and China showed that nicorandil has equivalent antianginal effects as nitrates,B-blockers and calcium-channel blockers. The clinical trials demonstrated that nicoramdil prevented anginal attacks and improved exercise capacity in patients with stable angina.The IONA and JCAD study showed a significant improvement in outcome due to a reduction in major coronary events or cardiovascular death with long-term administration of nicorandil in patients with stable angina. Nicorandil is well tolerated with only minor side effects such as headache, nausea, flushing and dizziness, without resistance. Oral ,anal and gastrointestinal ulceration induced by nicorandil has been reported. Conclusion： Nicorandil is a new class of well tolerated antiangina products with vasodilating and cardioprotective action. It is expected to have clinical effects that are different from the current antianginal drugs and to achieve management of angina that is poorly controlled by other drugs.