The actions of aminopyridines on avian muscle

The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle. All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release.