Analysis of new-generation neurosteroids in brain by LC/MS/MS coupled to derivatization with ESI-enhancing and deuterium-labeling reagents
| Project/Area Number |
26460043
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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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| Research Field |
Physical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 神経活性ステロイド / ESI増強重水素標識試薬 / LC/MS/MS / 精神・神経疾患 / アンドロゲン / ビタミンD代謝物 / 胆汁酸 / 創薬 / 分析科学 / 誘導体化試薬 / ESI増強 / 重水素標識 / 向精神薬 / アロプレグナノロン |
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| Outline of Final Research Achievements |
Qualitative and quantitative analyses of new-generation neurosteroids (NSs), such as androgens and bile acids, can contribute to the discovery and development of new antipsychotic agents and therapy for psychiatric disorders targeting neurosteroidogenesis. In this study, novel LC/MS/MS assays coupled to derivatization with the ESI-enhancing and deuterium-labeling reagents were developed. Using the developed method, we demonstrated the possibility that mianserin and mirtazapine elevate the brain allopregnanolone concentration and have anxiolytic effects. Three unconjugated bile acids (BAs), including chenodeoxycholic acid, were identified and quantified as the major BAs in the rat brain. Based on the comparison with their serum levels, we found that most BAs in the brain are derived from the periphery and the major mechanism for the transportation of the unconjugated BAs to the brain is the passive diffusion.
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Report
(4 results)
Research Products
(26 results)
