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2016 Fiscal Year Final Research Report

Analysis of new-generation neurosteroids in brain by LC/MS/MS coupled to derivatization with ESI-enhancing and deuterium-labeling reagents

Research Project

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Project/Area Number 26460043
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionTokyo University of Science

Principal Investigator

HIGASHI TATSUYA  東京理科大学, 薬学部薬学科, 教授 (90272963)

Project Period (FY) 2014-04-01 – 2017-03-31
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
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.

Free Research Field

臨床分析科学

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Published: 2018-03-22  

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