Post- and presynaptic effects of vesamicol (AH5183) on the frog neuromuscular junction.

The effects of vesamicol (AH5183), a blocker of acetylcholine transport, on the voltage-clamped neuromuscular junction of the frog were studied. Vesamicol (15-30 microM) reduced the peak height of the ionophoretically applied acetylcholine-induced current. The amplitude of the evoked endplate current was also decreased in the presence of vesamicol (30 microM). The endplate current was reduced further when the nerve was tetanically stimulated. The reduction of the endplate current after tetanic stimulation in the presence of vesamicol was due to a decrease in the mean quantal content. The decay time constants of the evoked endplate current and the miniature endplate current were also decreased by vesamicol. It was concluded that vesamicol acts as a postsynaptic blocker at the endplate. This neurotoxin could also decrease the immediately available quanta in the presynaptic nerve terminal, but the mechanism of action of vesamicol on transmitter release remains obscure.