Effect of Pancuronium Bromide on Acetylcholine Release 1

Pancuronium bromide had originally been shown by Buckett and Bonta in 1966 (1) and by Buckett et al. (2) in 1968 to have a nondepolarizing neuromuscular blocking action similar to curare. This was confirmed by Lewis et al. (3) in 1967. However, recently Sohn and Aldrete (4) have suggested that the drug might be acting presynaptically. The purpose of this work was to test the hypothesis that this agent did in fact act presynaptically. If it does then it should affect the acetylcholine release from the nerve terminal.

Methods. Bioassay of acetylcholine. The amount of acetylcholine released in the frog sciatic nerve gastrocnemius muscle preparation was bioassayed on the guinea pig ileum according to the method described by Gergis et al. (5).

Pancuronium bromide was added to the medium bathing the nerve muscle preparation in different concentrations and the amount of acetylcholine released, with or without nerve stimulation, was measured.

In another group of experiments, the effect of tetrodotoxin, high magnesium, low calcium, and hemicholinium on pancuronium-treated nerve muscle preparation was studied. The first three agents were tested without nerve stimulation, while with hemicholinium the nerve was stimulated until there was a 50% reduction in muscle twitch height, then stimulation was stopped, and pancuronium was added.

In all cases, two preparations were obtained from each animal, one was tested for the particular experimental procedure while the other served as its control.

Statistics. For most comparisons Student's t test or analysis of variance was used (6). In all cases the level of probability was p≤.05.

Results. Pancuronium bromide in concentrations ranging from 0.003 to 0.1 μg/ml produced a dose-related increase in the acetylcholine release in the nonstimulated muscle preparation (Fig. 1). There was no further increase in the acetylcholine release when the drug was added to the indirectly stimulated muscle preparation.