Micheli D, Collodel A, Semeraro C, Gaviraghi G, Carpi C
Glaxo Research Laboratories, Verona, Italy.
J Cardiovasc Pharmacol. 1990 Apr;15(4):666-75.
Lacidipine, currently being evaluated as a once-daily antihypertensive agent, acted as a calcium entry blocker on rabbit ear artery (pA2 = 9.4) with a markedly slower onset of action than that of nitrendipine; this effect was not reversed after 9 h of drug washout. Calcium entry blocker activity was also evaluated on nonvascular smooth muscles: Lacidipine showed a more pronounced vascular selectivity than nitrendipine; for both drugs, concentrations required to induce negative inotropic effects in guinea pig ventricular strip were approximately 100 times higher than concentrations needed to antagonize calcium contraction in vascular smooth muscle. In spontaneously hypertensive rats (SHR), by the tail-cuff method, lacidipine (ED25 = 0.35 mg/kg orally, p.o.) proved approximately 30 times more potent, slower in onset, and longer-acting than nitrendipine in reducing blood pressure. These features were confirmed in chronically implanted SHR after oral and intravenous (i.v.) administration (ED25 = 0.19 mg/kg p.o. and 0.006 mg/kg i.v.). A short-lasting tachycardia was detected with both drugs. No evidence of acquired tolerance emerged after repeated oral administrations over a 3-week period. Lacidipine induced a natriuretic effect in saline-loaded SHR at antihypertensive doses. In renal hypertensive dogs, lacidipine proved more potent (three to seven times), slower in onset, and longer-lasting than nitrendipine after p.o. (ED25 = 0.22 mg/kg) and i.v. (ED25 = 0.004 mg/kg) administrations.
拉西地平目前作为一种每日一次的抗高血压药物正在进行评估，它对兔耳动脉起钙通道阻滞剂的作用（pA2 = 9.4），起效明显比尼群地平慢；药物洗脱9小时后这种作用仍未逆转。还对非血管平滑肌的钙通道阻滞剂活性进行了评估：拉西地平显示出比尼群地平更显著的血管选择性；对于这两种药物，在豚鼠心室条带中诱导负性肌力作用所需的浓度比拮抗血管平滑肌中钙收缩所需的浓度高约100倍。在自发性高血压大鼠（SHR）中，通过尾套法，拉西地平（口服ED25 = 0.35 mg/kg）在降低血压方面比尼群地平效力高约30倍，起效慢且作用持久。口服和静脉注射（i.v.）给药后（口服ED25 = 0.19 mg/kg，静脉注射ED25 = 0.006 mg/kg），在长期植入的SHR中证实了这些特征。两种药物均检测到短暂的心动过速。在3周内重复口服给药后未出现获得性耐受性的证据。拉西地平在抗高血压剂量下对盐水负荷的SHR有排钠作用。在肾性高血压犬中，口服（ED25 = 0.22 mg/kg）和静脉注射（ED25 = 0.004 mg/kg）后，拉西地平比尼群地平效力更强（3至7倍），起效慢且作用更持久。
