Protective Effect of GTS-21, a Novel Nicotinic Receptor Agonist, on Delayed Neuronal Death Induced by Ischemia in Gerbils

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The neuroprotective effects of GTS-21 [3-(2, 4-dimethoxybenzylidene)-anabaseine dihydrochloride] were studied and compared with those of nicotine, 9-amino-1, 2, 3, 4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB) using a cerebral ischemia model in Mongolian gerbils. The learning performance and memory retention were elucidated by a step-through passive avoidance task at 2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated gerbils showed impairment of learning performance and memory retention. Neuronal cell death in the hippocampal CA1 area was observed at 7 days after ischemia. When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (-)-nicotine (1.5 mg/kg), THA (5 mg/kg) and PB (50 mg/kg) significantly attenuated the impairment of passive avoidance performance and the neuronal cell death induced by the ischemia. When administered orally twice daily for 2 weeks prior to the ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal cell death, while (-)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the amnesia. These results suggest that GTS-21 exerts a protective activity on not only impairment of learning and memory but also delayed neuronal death and that the underlying mechanism of GTS-21 differs from that of nicotine or THA.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 76(1), 23-29, 1998-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008190984
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4395854
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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