A study on concomitant drugs to improve the analgesic effects and decrease the side effects of morphine
| Project/Area Number |
25460227
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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 |
Medical pharmacy
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
Kagaya Hajime 明治薬科大学, 薬学部, 教授 (00642969)
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| Co-Investigator(Kenkyū-buntansha) |
UESAWA Yoshihiro 明治薬科大学, 薬学部, 准教授 (90322528)
NOZAWA Reiko (ISHII Reiko) 明治薬科大学, 薬学部, 講師 (60257144)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | モルヒネ / 併用薬 / 定量的構造活性相関 / 機械学習 / 血液脳関門 / トランスポーター / 鎮痛効果 / コンパニオンドラッグ |
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| Outline of Final Research Achievements |
Morphine is a substrate of MDR1, which is expressed in the BBB and regulates the excretion of drugs from the brain. On the other hand, morphine-6-glucuronide (M-6-G), an active metabolite, is a substrate of OATP. Therefore, seed compounds for concomitant drugs with morphine were investigated to identify compounds that can prohibit the elimination of morphine by MDR1 and allow the uptake of M-6-G by OATP. Compounds with properties similar to OATP1A2 substrates and MDR1 inhibitors were extracted from drug interaction databases. Structural properties were calculated based on chemical structures to construct QSAR models. The models were constructed using machine learning techniques, such as deep-learning. The models for both transporters were adopted to locate seed compounds from a chemical compound database to ensure that the morphine reached the brain effectively. These models enabled the selection of compounds with the dual properties of high MDR1 inhibition and low OATP substrate.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] 回復期リハビリテーション病棟における薬剤師常駐の必要性と医師・看護師の潜在的なニーズの探索2015
Author(s)
藤原 久登, 濃沼 政美, 湯本 哲郎, 前田 拓哉, 上手 真梨子, 河原 英子, 添田 真司, 瀧本 淳, 田村 和敬, 中村 雅敏, 金田 光正, 高尾 良洋, 齋藤 昌久, 加賀谷 肇, 村山 純一郎
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Journal Title
薬学雑誌
Volume: 135
Pages: 969-975
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Quantitative structure-cytotoxicity relationship of piperic acid amides2014
Author(s)
Shimada C, Uesawa Y, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Takao K, Miyashiro T, Sugita Y, Sakagami H
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Journal Title
Anticancer Res.
Volume: 34
Pages: 4877-4884
NAID
Related Report
Peer Reviewed
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[Journal Article] Quantitative structure-cytotoxicity relationship of 3-styrylchromone2014
Author(s)
Uesawa Y, Ishii-Nozawa R, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Takao K, Sugita Y, Sakagami H
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Journal Title
Anticancer Res.
Volume: 34,
Pages: 5405-5411
NAID
Related Report
Peer Reviewed
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[Journal Article] Investigation of the Safety of Topical Metronidazole from a Pharmacokinetic Perspective2013
Author(s)
Iid J, Kudo T, Shimada K, Yasuno Y, Yamagishi S, Hasegawa S, Ike H, Sato T, Kagaya H, Ito K
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 36
Issue: 1
Pages: 89-95
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed
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