Actions of 4-methyl-2-aminopyridine on neuromuscular transmission and contractility of skeletal muscle.

4-Methyl-2-aminopyridine (4M2AP) increased responses of isolated rat diaphragm and chick biventer cervicis nerve-muscle preparations to nerve stimulation but depressed responses to direct stimulation. Responses to acetylcholine were also increased while responses to carbachol were depressed. When tested after inhibition of acetylcholinesterase activity with neostigmine the effect of 4M2AP on responses to indirect stimulation was greatly reduced and responses to acetylcholine were depressed. It is concluded that, in contrast to other aminopyridines, 4M2AP facilitates neuromuscular transmission by inhibition of cholinesterase rather than augmenting release of acetylcholine and depresses rather than enhances muscles contractility.