| Project/Area Number |
16K08354
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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 |
Environmental and hygienic pharmacy
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| Research Institution | Daiichi University, College of Pharmaceutical Sciences |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 危険ドラッグ / HU-210 / HU-211 / 代謝 / 細胞毒性 / シトクロムP450 / CYP発現系 / ヒト肝ミクロソーム / CYP3A4 / JWH-018 / JWH-073 / 合成CB受容体アゴニスト / delta-9,11-THC / CYP / ＣＹＰ |
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| Outline of Final Research Achievements |
1)Among 13 synthetic cannabinoids examined, JWH-018, JWH-073, JWH-133, AM251, SR144,528, Rimonabant, delta-9,11-THC, HU-210 and HU-211 exhibited Type I spectra with human liver microsomal cytochrome P450 (CYP).2)Delta-9,11-THC showed more potent cytotoxic effect to MCF-7 cell compared to delta-9-THC.3)HLMs metabolism of HU-210role andHU-211 was studied, and important role of CYP3A4 was clarified.4)Synthetic cannabinoids, JWH-018、JWH-073、HU-211、WIN-55212-1 and WIN-55212-2 induced differentiation of 3T3-L1 cell to adipocyte cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた成果は、合成CB受容体アゴニスト（特にJWH-018, JWH-073, HU-210など）のヒトカンミクロソームによる代謝を明らかにしたものであり、関与するCYP分子種の情報や細胞毒性も含めて、薬物相互作用や薬理毒性などの健康被害を考える上で有用な基礎的な知見を与える学術的意義がある。また、代謝の情報は関連薬物を生体試料から検出する際に極めて重要であり、社会的意義を有するものと考えられる。
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