Vascular-selective effect of lercanidipine and other 1,4-dihydropyridines in isolated rabbit tissues

The aim of this study was to characterize the in-vitro vasoselectivity of l ercanidipine tin comparison with lacidipine, amlodipine, nitrendipine and f elodipine) by evaluating its functional calcium antagonistic activity on ra bbit vascular (aorta) and cardiac tissues (heart ventricle). Although incubation with all the compounds tested elicited a concentration- dependent relaxant effect on vascular tissue precontracted with KCl (80 mM) , 50% relaxation was reached at different times for each concentration and drug tested. At 10 nM concentration 50% relaxation was reached after 210 mi n with lercanidipine, 278 min with amlodipine, 135 min with lacidipine, 75 min with nitrendipine and 70 min with felodipine. The onset of the effect w as, therefore, similar for lercanidipine, amlodipine and lacidipine, but fa ster for nitrendipine and felodipine. Similarly, all the compounds tested c oncentration-dependently reduced the force of cardiac contraction (negative inotropic activity). Tn this model, the time needed to re ach 50% reductio n in contractile force was also concentration-dependent, and the ranking or der of the speed of onset of the effect (evaluated as the ratio of the IC50 values (the concentrations inhibiting contraction by 50%) calculated after 1 and 4 h incubation) was lacidipine (3.8) >amlodipine (9.6) >felodipine ( 39) >lercanidipine (68) = nitrendipine (89). The vasoselectivity, expressed as the ratio of the IC50 values obtained on cardiac and vascular tissue, w ere (for 4 h incubation) 730, 193, 95, 6 and 3 for lercanidipine, lacidipin e, amlodipine, felodipine and nitrendipine, respectively, showing that lerc anidipine is the most vasoselective of the calcium-antagonists tested. The results show that lercanidipine reduces the inotropic force of the rabb it heart to a lesser extent than do other calcium antagonists, and that thi s drug had the best heart/vessel selectivity index among the compounds test ed at all the times tested.