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

1 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. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) 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. 3 4-APMI (10(-4) M) prolonged the time courses of endplate potentials (e.p.ps) and miniature endplate potentials (m.e.p.ps) in the frog. 4 4-APMI (10(-4) M) 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. 5 4-APMI (10(-3) to 3 X 10(-3) M) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle. 6 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.