Guanidines pp 125-133 | Cite as

The Effect of Sodium Valproate on Blood Ammonia Levels and the Concentrations of Guanidino Compounds in Mouse Tissue

  • Jium Shiou Chang
  • Yoko Watanabe
  • Akitane Mori


Sodium valproate (SVA) is an anticonvulsant drug which has been widely used for the treatment of epilepsy. Recently it was reported that SVA has hepatic toxicity1,2,3,4 and induces hyperammonemia in humans5,6,7,8. These reports prompted us to suspect that SVA might affect guanidino compound metabolism as well as nitrogen metabolism. In the present study we investigated the effect of SVA on both blood ammonia levels and the concentrations of guanidino compounds in the liver, kidney, pancreas, brain, plasma and urine of mice who were administered SVA intraperitoneally.


Valproic Acid Urea Cycle Sodium Valproate Blood Ammonia Level Guanidino Compound 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. F. Donat, J. A. Bocchini, E. Gonzalez and R. N. Schwendimann, Valproic acid and fatal hepatitis, Neurology 29: 273 (1979).Google Scholar
  2. 2.
    F. J. Suchy, W. F. Balistreri, J. J. Buchino, J. M. Soneimer, S. R. Bates, G. L. Kearns, J. D. Stull and K. E. Bove, Acute hepatic failure associated with the use of sodium valporate, N. Engl. J. Med. 300:962 (1979).Google Scholar
  3. 3.
    T. A. Bowdle, I. H. Patel, A. J. Wilensky and C. Comfort, Hepatic failure from valproic acid, N. Engl. J. Med. 301:435 (1979).Google Scholar
  4. 4.
    N. Gerber, R. G. Dickinson, R. C. Harland, R. K. Lynn, D. Houghton, J. I. Antonias and J. C. Schimschock, Reyelike syndrome associated with valproic acid therapy, J. Pediatr. 95:142 (1979).Google Scholar
  5. 5.
    D. L. Coulter and R. J. Allen, Hyperammonemia with valproic acid therapy, J. Pediatr. 99:317 (1981).Google Scholar
  6. 6.
    S. Rawat, W. J. Borkowski and H. M. Swick, Valproic acid and secondary hyperammonemia, Neurology 31: 1173 (1981).Google Scholar
  7. 7.
    M. L. Batshaw and S. W. Brusilow, Valproate-induced hyperammonemia, Ann. Neurol. 11:319 (1982).Google Scholar
  8. 8.
    A. Mori, Y. Watanabe and N. Fujimoto, Fluorometrical analysis of guanidino compounds in human cerebrospinal fluid, J. Neurochem. 38:448 (1982).Google Scholar
  9. 9.
    Y. Watanabe, S. Shindo and A. Mori, Developmental changes in guanidino compound levels in mouse organs (in this book).Google Scholar
  10. 10.
    F. X. Coude, D. Rabier, L. Cathelineau, G. Grimber, P. Parvy and P. Kamoun, A mechanism for valproate-induced hyperammonemia, in:“Urea Cycle Diseases,” A. Lowenthal, A. Mori and B. Marescau, eds., Plenum Press, New York (1982).Google Scholar
  11. 11.
    S. Shindo, Y. Watanabe, Y. Katayama and A. Mori, Effects of electroconvulsive shock and ammonium acetate on guanidino compounds in the mouse brain, Neurdsciences 8: 347 (1982).Google Scholar
  12. 12.
    S. Natelson, A. Koller, H. Tseng and R. F. Dods, Canaline corbamoyltransferase in human liver as part of a metabolic cycle in which guanidino compounds are formed, Clin, Chem. 23:960 (1977).Google Scholar
  13. 13.
    B. D. Cohen and H. Patel, Guanidinosuccinic acid and the alternate urea cycle, in:“Urea Cycle Diseases,” A. Lowenthal, A. Mori and B. Marescau, eds., Plenum Press, New York (1982).Google Scholar
  14. 14.
    G. Perez and R. Faluotico, Creatinine: A precursor of methyl-guanidine, Expérientia 29: 1473 (1973).Google Scholar
  15. 15.
    H. Mikami, Y. Orita, A. Ando, M. Fujii, T. Kikuchi, K. Yoshihara, A. Okada and H. Abe, Metabolic pathway of guanidino compounds in chronic renal failure, in:“Urea Cycle Diseases,” A. Lowenthal, A. Mori and B. Marescau, eds., Plenum Press, New York (1982).Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Jium Shiou Chang
    • 1
  • Yoko Watanabe
    • 1
  • Akitane Mori
    • 1
  1. 1.Department of Neurochemistry, Institute for neurobiologyOkayama University Medical SchoolOkayama 700Japan

Personalised recommendations