Gille Andreas, Bodor Erik T, Ahmed Kashan, Offermanns Stefan
Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.
Annu Rev Pharmacol Toxicol. 2008;48:79-106. doi: 10.1146/annurev.pharmtox.48.113006.094746.
Pharmacological doses of nicotinic acid induce a profound change in the plasma levels of various lipids and lipoproteins. The ability of nicotinic acid to strongly increase the plasma concentration of high-density lipoprotein (HDL) cholesterol has in recent years led to an increased interest in the pharmacological potential of nicotinic acid. There is increasing evidence that nicotinic acid alone or in addition to LDL cholesterol-lowering drugs can reduce the progression of atherosclerosis and reduce the risk of cardiovascular events. The clinical use of nicotinic acid is, however, hindered by harmless but unpleasant side effects, especially by a strong cutaneous vasodilation called flushing. The recent discovery of the G protein-coupled receptor GPR109A (HM74A or PUMA-G) as a receptor for nicotinic acid has allowed for better understanding of the mechanisms underlying the metabolic and vascular effects of nicotinic acid. On the basis of recent progress in understanding the pharmacological effects of nicotinic acid, new strategies are in development to better exploit the pharmacological potential of nicotinic acid. New drugs acting via the nicotinic acid receptor or related receptors, as well as new co-medications that suppress unwanted effects of nicotinic acid, will most likely be introduced as new therapeutic options in the treatment of dyslipidemia and the prevention of cardiovascular diseases.
药理剂量的烟酸可引起各种脂质和脂蛋白血浆水平的深刻变化。近年来，烟酸显著提高高密度脂蛋白（HDL）胆固醇血浆浓度的能力引发了人们对其药理潜力的更多关注。越来越多的证据表明，单独使用烟酸或与降低低密度脂蛋白胆固醇的药物联合使用，均可减缓动脉粥样硬化进程并降低心血管事件风险。然而，烟酸的临床应用受到一些无害但令人不适的副作用的阻碍，尤其是一种称为潮红的强烈皮肤血管扩张。最近发现G蛋白偶联受体GPR109A（HM74A或PUMA-G）是烟酸的受体，这有助于更好地理解烟酸代谢和血管效应的潜在机制。基于对烟酸药理作用理解的最新进展，正在开发新的策略以更好地挖掘烟酸的药理潜力。通过烟酸受体或相关受体起作用的新药，以及抑制烟酸不良作用的新辅助药物，很可能会作为治疗血脂异常和预防心血管疾病的新治疗选择被引入。
