Neuroprotective Effect of YM-39558, Orotic Acid Ethylester, in Gerbil Forebrain Ischemia

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Author(s)

    • Akiho Hiraku AKIHO Hiraku
    • Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • Iwai Akihiko IWAI Akihiko
    • Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • TSUKAMOTO Shin-ichi
    • Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • KOSHIYA Kazuo
    • Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • YAMAGUCHI Tokio
    • Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

Abstract

We studied the effects of orotic acid and YM-39558 (2, 6-dioxo-1, 2, 3, 6-tetrahydropyrimidine-4-carboxylic acid ethyl ester), orotic acid ethylester, on delayed neuronal death of hippocampal CA1 neurons induced by transient forebrain ischemia. Our data indicated that YM-39558 had high permeability across the blood brain barrier and was hydrolyzed to orotic acid, the active substance, in the brain. The neuronal damage was reduced significantly in animals intraperitoneally treated with YM-39558 (100 mg/kg×3) after ischemia, but not with orotic acid in the same way. The results also suggested that the maintenance of a few ten micromolar orotic acid in cerebrospinal fluid were needed for its neuroprotective effects.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(4), 441-444, 1998-04-01

    The Japanese Pharmacological Society

References:  14

Codes

  • NII Article ID (NAID)
    10008192785
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    SHO
  • ISSN
    00215198
  • NDL Article ID
    4462602
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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