LACIDIPINE - A CALCIUM-ANTAGONIST WITH POTENT AND LONG-LASTING ANTIHYPERTENSIVE EFFECTS IN ANIMAL STUDIES

被引:66
作者
MICHELI, D
COLLODEL, A
SEMERARO, C
GAVIRAGHI, G
CARPI, C
机构
[1] Glaxo Research Laboratories, Verona
[2] Simes Cardiovascular Research Centre, Milan
关键词
Antihypertensive activity; Lacidipine; Natriuretic activity; Nitrendipine; Vascular and cardiac muscle;
D O I
10.1097/00005344-199004000-00020
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 -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 -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. © 1990 Raven Press, Ltd., New York.
引用
收藏
页码:666 / 675
页数:10
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