5-HT1A agonists, ameliorate movement disorder via non-dopaminergic systems in Parkinson's patients.
| Project/Area Number |
15590121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
MATSUBARA Kazuo Asahikawa Med.College, Department of Hospital Pharm.acy, Professor, 医学部, 教授 (20127533)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Keiko Asahikawa Med.College, Department of Legal Med., 医学部, 助教授 (90312462)
TASAKI Yoshikazu Asahikawa Med.College, Department of Hospital Pharm.acy, 医学部, 助教授 (60374807)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Parkinson disease / 5-HT1A receptor agonist / Tandospirone / extrapyramidal system / basal ganglia / 5HT1A受容体作動 / SH-SY5Y細胞 / 保護効果 / 細胞死 / 片側パーキンソン病モデル / グルタミン醜 / マイクロダイアリシス / 5HT1A受容体作動薬 / ラット |
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| Research Abstract |
Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their highest concentrations in the frontal cortex, subthalamic nucleus and entopeduncular nucleus as well as the dorsal and median raphe nucleus. There is growing evidence that 5-HT1A receptor agonists have an antidepressant effect in individuals with major depressive disorders. Recent clinical studies suggest that tandospirone, a highly potent and selective 5-HT1A receptor agonist used clinically as an antidepressant in Japan and China, may act as an antiparkinsonian drug. In the present study, we investigated the effect of tandospirone on contralateral rotational behavior in a unilateral hemiparkinsonian rat model produced with 6-hydroxydopamine (6-OHDA). Tandospirone, as well as 8-hydroxy-2-(di-n-propylamino) tetralin, significantly increased contralateral turnings in a dose-dependent manner (0.5-10 mg/kg). Tandospirone also remarkably potentiated the contralateral turning induced by 0.025 mg/kg of apomorphine. Pretreatment with WAY-100635, a 5-HT1A antagonist, almost completely blocked the contralateral turning behavior evoked by tandospirone, but not that by apomorphine. These results suggested that tandospirone could act on postsynaptic 5-HT1A receptors and modulate excitatory amino acid pathways in the basal ganglia. Thus, tandospirone could have therapeutic potential for the treatment of Parkinson's disease by modulating neuronal activities of non-dopaminergic pathways.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.2006
Author(s)
K.Matsubara, K Shimizu, M Suno, K.Ogawa, T.Awaya, T.Yamada, T.Noda, M.Satomi, K.Ohtaki, K.Chiba, Y.Tasaki, H.Shiono
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Journal Title
Brain Research (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.2004
Author(s)
K.Ohtaki., K.Matsubara, S.Fujimaru, K.Shimizu, T.Awaya, M.Suno, K.Chiba, N.Hayase, H.Shiono
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Journal Title
Journal of Neural Transmission 12
Pages: 1523-1535
Description
「研究成果報告書概要(欧文)」より
Related Report
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