Abstract

Bretylium and guanethidine had a postsynaptic blocking action at nerve-muscle junctions in rat diaphragm and frog sartorius preparations. This action was indicated by the ability of these drugs to reduce the amplitude of end-plate potentials and miniature end-plate potentials without affecting the extracellularly recorded presynaptic nerve action potential or the muscle membrane potential. Responses to acetylcholine (ACh) in the presence of neostigmine were also reduced by these drugs in both frog rectus abdominis and chick biventer cervicis preparations. It was felt that this effect was not the main cause of neuromuscular block by these drugs. In the case of bretylium the main cause was demonstrated to be a reduction of the release of ACh from motor nerve endings upon nerve stimulation. The intensification of neuromuscular block by increasing the stimulus rate and the rapid decline of the amplitude of successive end-plate potentials on repetitive stimulation suggest that the presynaptic effect of bretylium is hemicholinium-like. In the case of guanethidine the main effect appeared to be on muscle fibers. Contractile responses to direct muscle stimulation were reduced by this drug and the form of muscle action potentials was changed. It is concluded that bretylium and guanethidine have entirely different effects on the cholinergic system of the skeletal muscle.