European Journal of Pharmacology vol:357 issue:1 pages:93-105
The two novel dihydropyridines, oxodipine and elgodipine greatly depressed the KCl-induced contraction of rabbit aorta and decreased the cardiac force of contraction of rat ventricular strips with lower potency. Both compounds markedly shortened cardiac action potentials. In rat cultured neonatal ventricular myocytes, oxodipine and elgodipine decreased the L-type Ca2+ current (I-CaL) with IC50 of 0.24 and 0.33 mu M respectively while oxodipine was slightly more potent on the T-type Ca2+ current (I-CaT) than elgodipine (IC50 = 0.41 vs. 2.18 mu M) Both compounds were less potent in inhibiting I-CaL of adult cardiomyocytes. Oxodipine exhibited mostly a tonic block of both currents while elgodipine induced mainly a use-dependent block. Oxodipine and elgodipine increased by at least one order of magnitude their inhibitory potency on I-CaT and I-CaL when the cells were partially depolarized. We conclude that the mechanisms of inhibition of Ca2+ channels by these two dihydropyridines are different and suggest that the underlying mechanism of vascular selectivity is the voltage-dependent block of I-CaL, with the use-dependent inhibition of Ca2+ currents by elgodipine further contributing to this selectivity. (C) 1998 Elsevier Science B.V. All rights reserved.