Relative negative inotropic potencies of nine calcium channel blockers in cultured heart cells.

The direct inhibitory effects on contractility and beating rate of the calcium channel blockers diltiazem, verapamil and dihydropyridine derivatives nicardipine, nifedipine, nitrendipine, PY 108-068, (+/- ) PN 200-110 and its 2 stereoisomers, were compared in cultured chick embryo ventricular cells. In spontaneously beating cells, the negative inotropic and chronotropic potencies of nicardipine, nifedipine, nitrendipine and PY 108-068 were not significantly different. The inhibitory effects of verapamil, nifedipine and nicardipine were studied in cells electrically driven at a frequency close to their spontaneous beating rate: verapamil, nifedipine and nicardipine had similar negative chronotropic potencies; when the rate of stimulation was increased 1.5 and 2-fold, a frequency-dependent inhibitory effect on contraction was shown for verapamil, but not for nifedipine and nicardipine. Therefore, in our model, where the effects of beating rate on the amplitude of contraction were taken into account, no significant difference in the direct negative inotropic potenties of nifedipine and nicardipine was shown.