Effect of bretylium on neuromuscular transmission

The effect of bretylium on the response of an isolated muscle (guinea pig lumbrical) to direct and indirect stimulation was examined. An initial increase in twitch response to both indirect and direct stimulation was followed at higher concentrations of bretylium by block of the indirect response only. The ED50 for this latter effect was 106.9 +/- 9.25 microM. However, in the presence of subthreshold levels of d-tubocurarine the ED50 was markedly reduced to 1.31 +/- 1.11 microM, a concentration that could occur during clinical use of bretylium. Thus, the physician is cautioned to consider the possibility that neuromuscular block may be produced when bretylium is administered in close temporal proximity to neuromuscular blocking agents.