Mechanism of MJ 1999-induced blockade of neuromuscular transmission

MJ 1999 [4-(isopropylamino-1-hydroxyethyl)methanesulphonanilide hydrochloride] produced a dose-related blockade of indirectly evoked twitches of the rat diaphragm, without materially altering the effects of direct stimulation. The magnitude of blockade was comparable whether the indirect stimulation was at 1/s or 1/20 s. The blockade was less pronounced at 25° than at 34°. The blockade was antagonized by neostigmine, potassium chloride, succinyl-choline, tetraethylammonium, adrenaline, isoprenaline and, to some extent, by noradrenaline. Blockade by MJ 1999 was additive to that due to tubocurarine; large concentrations of yohimbine, tolazoline, phenoxybenzamine and dihydroergotamine quickly antagonized MJ 1999 blockade. Small concentrations of adrenaline, isoprenaline, tolazoline or yohimbine prevented MJ 1999 blockade. MJ 1999 had no effect on nerve conduction. It is proposed that MJ 1999 has a two-fold mode of action at the neuromuscular junction; a curare-like effect and an action on β-receptors.