In Vitro and In Vivo Vascular Selectivity of Lercanidipine and Its Enantiomers

In this study we evaluated the in vitro and in vivo vascular selectivity of lercanidipine and its enantiomers compared with nifedipine, nitrendipine, and felodipine. The in vitro functional calcium antagonist activity of lercanidipine and its enantiomers was studied in different rat tissues as relaxing potency against tonic contractions induced by preincubation with KCl, and lercanidipine and its enantiomers proved more active in the vascular tissue than in nonvascular tissues. In contrast, nitrendipine exhibited almost the same potency in all tested tissues. In rabbit heart ventricular strips electrically driven, lercanidipine (and its enantiomers) showed a very weak negative inotropic activity, being 857- and 667-fold less potent than felodipine and nitrendipine, respectively. The in vivo effects of i.v. lercanidipine. nitrendipine, and nifedipine were studied in anesthetized dogs catheterized and continuously monitored for systemic blood pressure, heart rate, and the isovolumic contractility index dP/dtmax. At doses producing equal vasodilatation, lercanidipine affected cardiac ventricular contractility much less than nifedipine and nitrendipine. Considering together the in vitro and in vivo data, it can be reasonably stated that lercanidipine displays marked vascular selectivity, causing blood pressure but not cardiac inotropism to be reduced.