Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction.

BACKGROUND AND OBJECTIVES It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each): procainamide - 20 microg mL(-1) (Group I); rocuronium - 4 microg mL(-1) (Group II); and rocuronium - 4 microg mL(-1) and procainamide - 20 microg mL(-1) (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5) and in the denervated rat diaphragm (n = 5), observing the influence of procainamide in the response to acetylcholine. RESULTS Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% +/- 7.1% blockade, which represented a statistically significant difference (p = 0.0067) when compared with Group II (10.4% +/- 4.5%), which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.