Augmentation of succinylcholine-induced neuromuscular blockade by calcium channel antagonists.

The block of endplate currents (EPCs) by succinylcholine, in frog cutaneous pectoris muscles, is significantly potentiated by certain organic calcium channel antagonists, at concentrations at which the calcium channel antagonists have no effect on EPCs themselves. Succinylcholine alone blocked the current in a dose-dependent manner with an IC50 = 2.7 microM in voltage-clamped muscle fibers. The ability of succinylcholine to block endplate currents was potentiated by nicardipine (3.5- and 31-fold by 1 and 10 microM, respectively), by bepridil (4.3-fold by 1 microM), and by verapamil (7.7-fold by 10 microM). The dihydropyridine nifedipine (10 microM), did not potentiate the succinylcholine effect. Since the calcium channel antagonists do not affect endplate currents directly at these concentrations, a channel blocking or receptor antagonistic effect of these drugs is not indicated. We therefore suggest that the enhancement of block by succinylcholine may be due to the increased desensitization of the receptor. Furthermore, this enhancement of desensitization may explain the effects of these calcium channel antagonists seen in whole animal studies, where the contractures caused by acetylcholine and succinylcholine, applied systemically, are blocked.