Effect of diphenylhydantoin on neuromuscular synapse

Abstract

Disordered neuromuscular transmission was found in 2 patients receiving diphenylhydantoin (DPH) therapy for epilepsy. In case 1, there was also anemia and vitamin B12 deficiency; normal neuromuscular function returned when DPH was stopped and cyanocobalamine was administered. In case 2, a massive dose of DPH were administered, improvement followed reduction in dosage. An effect of DPH on the neuromuscular synapse was demonstrated in rat preparations. The doses were relatively large (over 10 mg/kg) but consistent with that in case 2. The first effect was competitive neuromuscular blockade which potentiated curare and was relieved by edrophonium. Larger doses caused further blockade which appeared to result from either end-plate depolarization or anticholinesterase activity.