AT_1拮抗剂研究进展及安全性  

Research progress and Safety of AT1 antagonist

作　　者：裴振峨[1] 

机构地区：[1]北京市药品不良反应监测中心,北京100024

出　　处：《中国药物警戒》2004年第2期14-16,共3页Chinese Journal of Pharmacovigilance

摘　　要：临床上普遍使用的血管紧张素转化酶(ACE)抑制剂具有良好的降压效果,但在应用中,许多患者出现干咳和水肿副反应。一些学者根据血管紧张素Ⅱ(AngⅡ)对心血管的作用是通过AT1受体来介导实现的,研制开发出AT1拮抗剂,它避免了ACEI抑制缓激肽和P物质的降解导致的非剂量相关性干咳和血管神经性水肿。通过对这类药物结构修饰与活性关系的研究,找出此类药物活性结构:能与受体形成氢键的1个或多个N原子中心;能与受体疏水性基团结合的亲脂性侧链或侧环;含有易电离的离子作用基团或羧基、羟甲基及强极性功能团羰基等。临床目前最常用的AT1拮抗剂是氯沙坦和缬沙坦。临床应用证实此类药物不良反应发生率低,如干咳、肾功能障碍、血管性水肿的发生率远低于依那普利,此类药物会成为临床上有前景的抗高血压药物。Angiotensin-converting enzyme (ACE) inhibitors significantly decrease blood pressure in clinic. But the typical nonproductive cough and angioedema, commonly leads to ACE inhibitors withdrawal in hypertensive therapy. Because ACE inhibitors and angiotensin II type 1 (AT1) receptor antagonists differ in their effects on angiotensin II formation and bradykinin degradation, the incidence of nonproductive cough and angioedema in clinic is largely lower in AT1 antagonists therapy than ACE inhibitors therapy. The quantitative structure-activity relationship(QSAR) of AT1 receptor antagonists shows that the indispensable structures for the activity are the active center with one or more Nitrogen which form hydrogen bond with AT1 receptor, the lipophilic chains or rings which combine with the lipophilic domain of AT1 receptor and that carboxyl or methylhydroxyl group with easy ionization or the carbonyl group with strong polarity. Now Losartan and Valsartan are two AT1 antagonists of commonly being used in clinic. It is hopeful that AT1 antagonists may have a magnificent foreground in hypertension therapy.

关 键 词：血管紧张素Ⅱ受体 AT1拮抗剂 结构修饰与活性 安全性 

分 类 号：R972.4[医药卫生—药品]