Burges R, Moisey D
Pfizer Central Research, Sandwich, Kent, United Kingdom.
Am J Cardiol. 1994 Jan 27;73(3):2A-9A. doi: 10.1016/0002-9149(94)90268-2.
Amlodipine is an intrinsically long-acting, vasoselective calcium antagonist structurally related to nifedipine, but with unique binding and pharmacologic properties that distinguish it from other agents of this class. Pharmacokinetic studies in animal models demonstrate a more prolonged half-life, high volume of distribution, and gradual elimination of amlodipine compared with that of other calcium antagonists. The presence of a basic side chain at the 2-position of the dihydropyridine ring renders the molecule > 90% ionized at physiologic pH and is believed to be primarily responsible for its markedly different pharmacologic and pharmacokinetic properties. Amlodipine has slow receptor binding kinetics that result in a gradual onset of action and may allow for less dependence on instantaneous plasma levels. Although amlodipine appears to bind to additional calcium channel recognition sites blocked by diltiazem and verapamil, it does not significantly depress heart rate nor does it produce significant negative inotropic effects or electrophysiologic disturbances. Preclinical studies indicate that amlodipine is a potent antihypertensive agent with natriuretic and diuretic properties that may enhance its ability to reduce blood pressure without attendant fluid retention.
氨氯地平是一种本质上长效的血管选择性钙拮抗剂，在结构上与硝苯地平相关，但具有独特的结合和药理特性，使其有别于该类的其他药物。动物模型中的药代动力学研究表明，与其他钙拮抗剂相比，氨氯地平的半衰期更长、分布容积更大且消除过程较为缓慢。二氢吡啶环2位上的碱性侧链使该分子在生理pH值下的离子化程度>90%，据信这主要是其显著不同的药理和药代动力学特性的原因。氨氯地平具有缓慢的受体结合动力学，导致起效逐渐，并且可能较少依赖即时血浆水平。尽管氨氯地平似乎与地尔硫䓬和维拉帕米所阻断的其他钙通道识别位点结合，但它不会显著降低心率，也不会产生明显的负性肌力作用或电生理紊乱。临床前研究表明，氨氯地平是一种强效抗高血压药物，具有利钠和利尿特性，这可能增强其降低血压的能力而不会伴随液体潴留。
