Determination of the active form of phenytoin

R. S. Morello, T. Begenisich, J. Z. Yeh

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The actions of phenytoin (DPH) on sodium channels of squid giant axons were investigated. DPH suppressed the sodium current whether it was applied internally or externally. When DPH was applied externally, its potency depended upon the pH of the external solution. Similarly, when DPH was applied internally, its potency depended on the pH of the internal solution. The potency of DPH increased when the pH of the solution was lowered and the potency was relatively insensitive to pH changes in the solution on the opposite side of the membrane. These results suggest that the weak acid DPH, that exists at physiological pH values in both anionic and neutral forms, acts as a neutral molecule. Our results are reasonably well described by a model wherein one neutral DPH molecular interacts with and blocks one sodium channel. We find an equilibrium constant for the interactions with normal axons to be about 57 μM.

Original languageEnglish (US)
Pages (from-to)156-161
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume230
Issue number1
StatePublished - 1984

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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