Activity-dependent depression of nerve action potential by phenytoin

The action of the anticonvulsant drug phenytoin was investigated on the responsiveness of isolated amphibian and human nerves to repetitive stimulation. At low frequencies of stimulation (0.5-25 Hz) the drug (at a concentration of 0.1 mM) had no notable effect on the compound nerve action potential. By contrast, at higher rates of stimulation (50-300 Hz), it produced a progressive decrease in amplitude and integral of the compound action potential. This effect was positively correlated with the frequency of nerve activation and was markedly enhanced by elevating the extracellular K+ concentration. Thus, phenytoin induces a use- and frequency-dependent depression of axon conduction, which may contribute to its preferential suppression of the spread of high-frequency seizure discharge in the brain.