Actions of bretylium tosylate at the neuromuscular junction.

1. The actions of bretylium tosylate on neuromuscular transmission in the rat phrenic nerve diaphragm preparation have been investigated by electrophysiological methods. Additional experiments have been made on the effect of the drug on the frog rectus preparation and on the acetylcholinesterase of erythrocytes.2. After bretylium, there was a reduction in the amplitudes of miniature end-plate potentials (mepps), endplate potentials (epps) and acetylcholine potentials recorded in the diaphragm, and also in the contractures of the rectus in response to acetylcholine (ACh) and to carbachol.3. After bretylium, there was a prolongation of the time courses of epps and ACh potentials. Under certain circumstances there was enhancement of the amplitudes of epps and ACh potentials and of the contractile responses to ACh but not to carbachol.4. Bretylium reduced the velocity of hydrolysis of ACh by erythrocyte ghosts. This inhibition was competitive and the Ki of bretylium was 0.053 mM.5. Bretylium did not cause a reduction in the mean quantal content of the epp in junctions blocked with Mg(++).6. It is concluded that bretylium exerts both facilitatory and inhibitory influences on neuromuscular transmission, which, exerted simultaneously, may give the false appearance that the drug has little action at this synapse.