2021 Fiscal Year Final Research Report
Development of novel neuroprotective oxicam derivatives for the treatment of Parkinson's disease
| Project/Area Number |
19K07186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | パーキンソン病進行抑制薬 / meloxicam誘導体の開発 / 新規治療薬候補 |
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| Outline of Final Research Achievements |
The aim of this study is to obtain novel derivatives of oxicams as candidate compounds for clinical trial of neuroprotective antiparkinsonian drugs. We have found two potential compounds which protect brain dopaminergic neuronal death in the mouse parkinsonian model, but these compounds were needed to improve potency of neuronal protection and brain permeability for clinical trials. We examined potency of neuroprotection and brain permeability for more than 40 newly synthesized compounds, but we didn't obtain improved potential compounds for clinical trial, compared to original two compounds. On the other hand immunohistological study of mouse brain slices of parkinsonian model treated by one of the original drugs clearly showed protection against dopaminergic neuronal death in the affected brain region of Parkinson's disease. This results showed the oxicam derivatives were the probable target of disease-modifying drugs for Parkinson's disease.
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| Free Research Field |
神経科学、医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
現在のパーキンソン病治療薬は、症状を改善する対症療法薬のみであり病気の進行を抑制できない。そのため長期に使用すると有効性の低減や変動が起こり問題となっており、本病気の進行抑制薬開発が強く望まれている。本研究は、すでに市販されている解熱鎮痛薬のメロキシカムとその誘導体がマウスパーキンソン病モデルでパーキンソン病の原因である脳ドパミン神経細胞死を抑制することを見出し、パーキンソン病進行抑制薬の開発へと進めていく研究である。今回の結果からマウスモデルでパーキンソン病で傷害される脳部位が誘導体により保護されていることが明らかとなり、進行抑制薬としての可能性が高まったと考えられる。
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