A comparison of the facilitatory actions of 4-aminopyridine methiodide and 4-aminopyridine on neuromuscular transmission

4‐Aminopyridine methiodide (4‐APMI), a quaternary analogue of aminopyridine (4‐AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve‐muscle preparations. In the chick, 4‐APMI (10⁻⁴ to 10⁻²m) augmented indirectly elicited twitches and reversed tubocurarine‐induced neuromuscular block. Reversal of tubocurarine block was observed after treatment of the muscle with an anticholinesterase. 4‐APMI did not itself produce contracture but augmented responses to added acetylcholine. 4‐APMI (10⁻⁴m) prolonged the time courses of endplate potentials (e.p.ps) and miniature end‐plate potentials (m.e.p.ps) in the frog. 4‐APMI (10⁻⁴m) increased e.p.p. quantal content. 4‐AP was about 100 times more active than 4‐APMI in increasing quantal content. Both compounds prolonged muscle action potentials at similar concentrations. 4‐APMI (10⁻³ to 3 × 10⁻³m) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle. It is concluded that 4‐APMI increases evoked acetylcholine release and also possesses a weak anticholinesterase action. The greater action of 4‐AP on quantal content is probably due to an intracellular action, possibly involving the release of calcium ions. 1979 British Pharmacological Society