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.
- antiepileptic drug
- frequency-dependence-action potential
- sciatic nerve
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