Pharmacology of lacidipine, a vascular-selective calcium antagonist.
Lacidipine is a new 1,4-dihydropyridine (DHP) that induces a potent calcium antagonistic activity on vascular preparations. It has a markedly slow rate of onset, but its effect is still apparent after 9 h of drug washout. Calcium antagonistic activity has been evaluated on nonvascular smooth muscle, and lacidipine has proved to be more vascular-selective than standard DHP derivatives. In cardiac preparations, the concentrations required to induce negative inotropic effects are approximately 100 times higher than concentrations needed to antagonize calcium-induced contractions in vascular smooth muscle. In addition, lacidipine exhibits antioxidant properties in tests based on the autoperoxidation of rat cerebral cortical membranes. In spontaneously hypertensive rats (SHRs), lacidipine induces a potent and long-acting blood pressure reduction (ED25 = 0.19 mg/kg orally and 0.006 mg/kg intravenously, with durations greater than 12 and 3 h, respectively). In saline-loaded SHRs and at antihypertensive dosages, lacidipine increases urine volume as well as urinary excretion of sodium. In one-clip, two-kidney renal hypertensive dogs, the antihypertensive properties of lacidipine after both oral and intravenous administration were confirmed. The marked vascular selectivity of lacidipine was clearly evident both in pithed rats infused with angiotensin II and in anesthetized dogs, in which preferential and long-lasting coronary and vertebral blood flow increases were also observed.
Micheli
D
D
Glaxo Research Laboratories, Glaxo SpA, Verona, Italy.
Ratti
E
E
Toson
G
G
Gaviraghi
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D051381:Rats
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine