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The cellular mode of action of the anti-epileptic drug 5, 5-diphenylhydantoin

Nature volume 272, pages 271–273 (1978)Cite this article

Abstract

THE molecular basis of the many effects of 5,5-diphenylhydantoin (DPH, Dilantin) remains obscure. In addition to being the drug of choice in the prevention of seizures1, DPH is used to correct cardiac arrhythmias (mainly those caused by digitalis)2, and to control myokymia (continuous muscle fibre activity)3, and excessive secretion of insulin4 or anti-diuretic hormone5. Side effects include hypotension, hyperglycaemia and disturbances of calcium homeostasis6. Among the actions proposed for DPH are stimulation of active sodium/potassium transport7, inhibition of passive sodium influx in stimulated (but not in resting) cells8,9, reduction of calcium influx10,11, and specific interference with synaptic transmitter movements12. We report here that DPH does not affect active sodium transport, but blocks passive resting sodium channels in much the same way as tetrodotoxin (TTX) does, and we suggest that from this elementary action may follow many of the drug's therapeutic, adverse, and in vitro effects.

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References

  1. Woodbury, D. M. & Fingl, E. in The Pharmacological Basis of Therapeutics 5th edn (eds Goodman, L. S. & Gilman, A.) 201–226 (Macmillan, New York, 1975).

    Google Scholar 

  2. Bigger, J. T., Jr Adv. intern. Med. 18, 251–281 (1972).

    PubMed  CAS  Google Scholar 

  3. Isaacs, H. & Frere, G. S. Afr. med. J. 48, 1601–1607 (1974).

    PubMed  CAS  Google Scholar 

  4. Cohen, M. S. et al. Lancet i, 40–41 (1973).

    Article  Google Scholar 

  5. Landolt, A. M. Acta endocr. Copenh. 76, 625–628 (1974).

    Article  CAS  Google Scholar 

  6. Richens, A. & Rowe, D. J. Br. med. J. 4, 73–76 (1970).

    Article  CAS  Google Scholar 

  7. Woodbury, D. M. J. Pharmac. exp. Ther. 115, 74–95 (1955).

    CAS  Google Scholar 

  8. Pincus, J. H. Archs Neurol. 26, 4–10 (1972).

    Article  CAS  Google Scholar 

  9. Lipicky, R. J., Gilbert, D. L. & Stillman, I. M. Proc. natn. Acad. Sci. U.S.A. 69, 1758–1760 (1972).

    Article  ADS  CAS  Google Scholar 

  10. Sohn, P. S. & Ferrendelli, J. A. J. Pharmac. exp. Ther. 185, 272–275 (1973).

    CAS  Google Scholar 

  11. Pincus, J. H. & Lee, S. H. Archs Neurol. 29, 239–244 (1973).

    Article  CAS  Google Scholar 

  12. Ayala, G. F., Johnston, D., Lin, S. & Dichter, H. N. Brain Res. 121, 259–270 (1977).

    Article  CAS  Google Scholar 

  13. De Weer, P. & Geduldig, D. Science 179, 1326–1328 (1973).

    Article  ADS  CAS  Google Scholar 

  14. Freeman, A. R. Comp. Biochem. Physiol. 40 A, 71–82 (1971).

    Article  CAS  Google Scholar 

  15. Hodgkin, A. L. & Keynes, R. D. J. Physiol., Lond. 128, 61–88 (1955).

    Article  CAS  Google Scholar 

  16. Schwarz, J. R. & Vogel, W. Eur. J. Pharmac. 44, 241–249 (1977).

    Article  CAS  Google Scholar 

  17. Baker, P. F. et al. J. Physiol., Lond. 200, 459–496 (1969).

    Article  CAS  Google Scholar 

  18. Neuman, R. S. & Frank, G. B. Can. J. Physiol. Pharmac. 55, 42–47 (1977).

    Article  CAS  Google Scholar 

  19. Narahashi, T. Physiol. Rev. 54, 813–889 (1974).

    Article  CAS  Google Scholar 

  20. Varga, E., Kovacs, T. & Szabo, B. Acta physiol. Hung. 41, 265–277 (1972).

    PubMed  CAS  Google Scholar 

  21. Matthews, E. K. & Sakamoto, Y. J. Physiol., Lond. 246, 439–457 (1975).

    Article  CAS  Google Scholar 

  22. Donatsch, P., Lowe, D. A., Richardson, B. P. & Taylor, P. J. Physiol., Lond. 267, 357–376 (1977).

    Article  CAS  Google Scholar 

  23. Guzek, J. W., Russell, J. T. & Thorn, N. A. Acta pharmac. tox. 34, 1–4 (1974).

    Article  CAS  Google Scholar 

  24. Gerich, J. E. et al. J. clin. Endocr. Metab. 35, 823–824 (1972).

    Article  CAS  Google Scholar 

  25. Pento, J. T. Horm. Metab. Res. 8, 399–401 (1976).

    Article  CAS  Google Scholar 

  26. Gutman, Y. & Boonyaviroj, P. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 296, 293–296 (1977).

    Article  CAS  Google Scholar 

  27. Blaustein, M. P. & King, A. C. J. Membr. Biol. 30, 153–173 (1976).

    Article  CAS  Google Scholar 

  28. Blaustein, M. P. Am. J. Physiol. 232, C165–C173 (1977).

    Article  CAS  Google Scholar 

  29. Esplin, D. W. J. Pharmac. exp. Ther. 120, 301–323 (1957).

    CAS  Google Scholar 

  30. Weinreich, D. J. Physiol., Lond. 212, 431–446 (1971).

    Article  CAS  Google Scholar 

  31. Shimizu, H., Creveling, C. R. & Daly, J. W. Molec. Pharmac. 6, 184–188 (1970).

    CAS  Google Scholar 

  32. Ferrendelli, J. A. & Kinscherf, D. A. Epilepsia 18, 331–336 (1977).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Washington University School of Medicine, St. Louis, Missouri, 63110

    J. GAVIN PERRY, LESLIE MCKINNEY & PAUL DE WEER

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  1. J. GAVIN PERRY
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  2. LESLIE MCKINNEY
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  3. PAUL DE WEER
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PERRY, J., MCKINNEY, L. & DE WEER, P. The cellular mode of action of the anti-epileptic drug 5, 5-diphenylhydantoin. Nature 272, 271–273 (1978). https://doi.org/10.1038/272271a0

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