Development of a Pyrrolidinone Derivative (Cyclic GABA) for Modulating Brain Glutamate Transmission

  • Kenji Matsuyama
  • Choichiro Miyazaki
  • Masataka Ichikawa
Part of the Advances in Behavioral Biology book series (ABBI, volume 36)


Senile Dementia of Alzheimer Type (SDAT) is a debilitating neurological disease that affects about one in six persons past the age of sixty (1,2). In spite of numerous hypotheses concerning the etiology of SDAT, e.g., abnormal blood aluminum levels (3), viral agents (4), genetic factors (5) and selective vulnerability of specific neuronal systems (6,7), its precise cause or causes remain unknown.


Passive Avoidance Gaba Level Shadowed Area Passive Avoidance Response Brain Gaba 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    C. Mckhann, D. Drachman, M. Folstein, R. Katzman, D. Price and E. M. Stadlan, Neurology 34, 939–944 (1984).CrossRefGoogle Scholar
  2. 2).
    Z. S. Khachaturian, Arch Neurol. 42, 1097–1105 (1985).CrossRefGoogle Scholar
  3. 3).
    D R. Crapper, S. S. Krishnan and S. Quittkat, Brain 99, 67–80 (1976).CrossRefGoogle Scholar
  4. 4).
    S. B. Prusiner, N Engl. J. Med, 310, 661–663 (1984).CrossRefGoogle Scholar
  5. 5).
    J. Constantinidis, in Alzheimer’s Disease: Senile Dementia and Related Disorders (R. Katzman, R. D. Terry and K. L. Bick, eds), pp.15–25 (Raven Press (1978).Google Scholar
  6. 6).
    P. J. Whitehouse, D. L. Price, A. W. Clark, J. T. Coyle and M. R. DeLong, Ann. Neurol 10, 122–126 (1981).CrossRefGoogle Scholar
  7. 7).
    P. L. McGeer, E. G. McGeer, J. Suzuki, C. E. Dolman and T. Nagai, Neuroloa’ 34, 741–745 (1984).CrossRefGoogle Scholar
  8. 8).
    P. Davies and A. J. F. Maloney, Lancet, ií, 1403 (1976).Google Scholar
  9. 9).
    T. D. Reisine, H. I. Yamamura, E. D. Bird, E. Spokes and S. J. Enna, Brain Res., 159, 477–481 (1977).CrossRefGoogle Scholar
  10. 10).
    J. T. Coyle, D. L. Price and M. A. DeLong, Science, 219, 1184–1190 (1983).CrossRefGoogle Scholar
  11. 11).
    D. M. Bowen, S. J. Allen, J. S. Benton, M. J. Goodhardt, E. A. Haan, A. M. Palmer, N. R. Sims, C. C. T. Smith, J. A. Spillance, M. M. Esiri, J. S. Snowdon, G. K. Wilcock and A. N. Davision,,Ty Neurochem. 41, 266–272 (1983).CrossRefGoogle Scholar
  12. 12).
    B. E. Tomlinson, D. Irving and G. Blessed, J. Neurol. Sci. 49, 419428 (1981).Google Scholar
  13. 13).
    J. T. Greenamyre, J. B. Penney, A. B. Young, C. J. D’Amato, S. P. Hicks, and I. Shoulson, Science 227, 1496–1499 (1985).CrossRefGoogle Scholar
  14. 14).
    J. T. Greenamyre, Arch Neurol. 43, 1058–1063 (1986).CrossRefGoogle Scholar
  15. 15).
    G. P. Wilkin, A. L. Hudson and D. R. Hill, Nature 294, 584–587 (1981).CrossRefGoogle Scholar
  16. 16).
    R. R. Goodman, M. J. Kuhar and L. Hester, Science 220, 967–969 (1983).CrossRefGoogle Scholar
  17. 17).
    S. J. Potashner and D. Gerard, J. Neurochem. 40, 1548–1557 (1983)CrossRefGoogle Scholar
  18. 18).
    A. C. Dolphin and E. R. Archer, Neurosci Lett. 43, 49–54 (1983).CrossRefGoogle Scholar
  19. 19).
    G. Bonanno and M. Raiteri, Neurosci. Lett., 70, 360–363 (1986).CrossRefGoogle Scholar
  20. 20).
    V. E. Shashoua, J. N. Jacob, R. Ridge, A. Campbell and R. Baldessarini, J. Med. Chem 27, 659–664 (1984).CrossRefGoogle Scholar
  21. 21).
    K. Matsuyama, C. Yamashita, A. Noda, S. Goto, H. Noda, Y. Ichimaru and Y. Gomita, Chem. Pharm. Bull. 32, 4089–4095 (1984).CrossRefGoogle Scholar
  22. 22).
    K. Matsuyama, C. Miyazaki, M. Ichikawa and S. Goto, Pharm. Res. submitted.Google Scholar
  23. 23).
    K. Matsuyama, C. Miyazaki, M. Ichikawa, S. Goto and J. Yamamoto, J Pharam. Dyn submitted.Google Scholar
  24. 24).
    C. Miyazaki, M. Ogasawara, M. Ichikawa, K. Matsuyama and S. Goto, J. Pharm. Dyn 11, 202–205, (1988).CrossRefGoogle Scholar
  25. 25).
    M. W. Brightman and T. S. Reese, J. Cell. Biol. 40, 648–677 (1969).CrossRefGoogle Scholar
  26. 26).
    J. D. Fenstermacher, R. G. Blasberg and C. S. Patlack, Pharmac. Ther 14, 217–248 (1981).CrossRefGoogle Scholar
  27. 27).
    H. H. Frey and W. Loscher, Neuropharmacoloax 19, 217–220 (1980).CrossRefGoogle Scholar
  28. 28).
    P. S. Callery, L. A Geelhaar, M. S. Balachandran, M. Stogniew and K. Gurudath Rao, J. Neurochem 38, 1063–1067 (1982).CrossRefGoogle Scholar
  29. 29).
    H. Bundgard, Design of Prodrugs, pp 64, Elsevier, Amsterdam (1985).Google Scholar
  30. 30).
    R. W. Olsen, J. Neurochem 37, 1–13 (1981).CrossRefGoogle Scholar
  31. 31).
    C. Giurgia, Actual Pharmacol 25, 115–156 (1972).Google Scholar
  32. 32).
    C. Miyazaki, K. Matsuyama, M. Ichikawa and S. Goto, Chem. Pharm. Beall. 36, 3589–3594 (1988).CrossRefGoogle Scholar
  33. 33).
    M. M. Cohen, Monogr Neural Sci. 1, 1–49 (1973).Google Scholar
  34. 34).
    C.Miyazaki, K. Matsuyama and M. Ichikawa, The Kyushu Neuro-psychiatry, in press.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Kenji Matsuyama
    • 1
  • Choichiro Miyazaki
    • 1
  • Masataka Ichikawa
    • 1
  1. 1.Department of Hospital PharmacyNagasaki University HospitalNagasaki 852Japan

Personalised recommendations