Phenytoin reduces frequency potentiation of synaptic potentials at the frog neuromuscular junction

The action of the commonly used antiepileptic drug phenytoin on frequency potentials was studied at the frog neuromuscular junction. Whereas the drug, at concentrations of 0.1-0.3 mM, had only a slight effect on EPPs evoked by nerve stimulation at a frequency of 0.5 Hz, it strongly suppressed their potentiation during tetanic nerve stimulation at 30 Hz. The post-tetanic potentiation of the EPPs was also reduced by the drug. These effects occurred without a blockade of invasion of the nerve impulse into the presynaptic terminal during the tetanus, and thus indicate a specific frequency-dependent depressant action of the drug on neurally-evoked transmitter release.