Effects of D-penicillamine on neuromuscular transmission in rats

Treatment of patients with D-penicillamine (D-P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D-P on neuromuscular transmission in rat muscle. In the first experiment, bath-applied D-P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D-P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D-P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D-P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia-like syndrome in humans.