Potentiation of neuromuscular blockade by verapamil

The effects of intravenous (iv) verapamil (0.01 to 1.0 mg/kg) on the constant neuromuscular block produced by an iv infusion of either pancuronium or succinylcholine were studied on the indirectly stimulated gastrocnemius and tibialis-anterior muscles of the rabbit anesthetized with halothane in oxygen. Verapamil alone (n = 6) had no significant effect. However, the drug did significantly potentiate the 50% twitch depression of the gastrocnemius muscle produced by a constant iv infusion of either pancuronium (n = 5) or succinylcholine (n = 5) to 36 +/- 6% and 45 +/- 1% of control, respectively. This effect of verapamil occurred with doses of 0.1 mg/kg for pancuronium and 0.01 mg/kg for succinylcholine; these doses of verapamil were the lowest which produced a significant effect. In contrast, verapamil had no significant effect on the progression of the neuromuscular blockade of either the gastrocnemius or tibialis-anterior muscles produced by alpha-bungarotoxin (n = 5). Verapamil also significantly prolonged the P-R interval of the ECG from a control value of 71 +/- 2 ms to 78 +/- 3 ms at a dose of 0.1 mg/kg and to 93 +/- 6 ms at a dose of 0.3 mg/kg. The possible mechanisms of the neuromuscular actions of verapamil are discussed and it is concluded that verapamil can produce potentiation of either pancuronium- or succinylcholine-induced neuromuscular block at doses within the therapeutic range.