THE EFFECT OF A THIAMINE ANALOG ON NEUROMUSCULAR TRANSMISSION

¹ Department of Physiology and Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York

The action of a thiamine analog, 3(4-amino-2-methyl pyrimidyl-5-methyl)-thiazolium bromide hydrobromide (AMPMT) on neuromuscular transmission has been studied on frog sciatic nerve-sartorius muscle preparations in vitro. Multifiber and single fiber techniques have been employed. AMPMT (10 x 10^-4 M) in 30 min depressed the tension output of indirectly stimulated muscle to 40% of the control value. The depression was not preceded by potentiation. AMPMT (5 x 10^-4 M) caused no significant depolarization of the muscle postjunctional membrane. It blocked neuromuscular transmission in 17 of 25 junctions. At blocked junctions end-plate potentials (e.p.p.'s) of low amplitude (average, 17.4 ± 1.8 mV) were recorded. The time course of these e.p.p.'s was not prolonged. At junctions in which transmission was not blocked, the rate of rise of the e.p.p. was significantly reduced. The critical membrane potential (at which level propagated action potentials were initiated) was unchanged by AMPMT. AMPMT (5 x 10^-4 M), when applied to desheathed frog sciatic nerve trunks, had no detectable effect on the wave-form of the compound action potential and no change in conduction velocity was produced. AMPMT (5 x 10^-4 M) reduced the sensitivity of the postjunctional membrane to applied acetylcholine six- to eight-fold. The neuromuscular blocking action of AMPMT is largely explainable on the basis of this inhibitor action at the postjunctional membrane. AMPMT at first weakly antagonizes and then potentiates a neuromuscular block produced by d-tubocurarine. In producing a neuromuscular block, AMPMT is 350 to 400 times less potent than d-tubocurarine. Thus AMPMT would seem to have little value as a muscular relaxant in anesthesiologic practice.