• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

A study on concomitant drugs to improve the analgesic effects and decrease the side effects of morphine

Research Project

Project/Area Number 25460227
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

Kagaya Hajime  明治薬科大学, 薬学部, 教授 (00642969)

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)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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
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.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (42 results)

All 2016 2015 2014 2013

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (21 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results) Book (4 results)

  • [Journal Article] Electron Ionization Mass Spectrometry-based Metabolomics Studies of Sophoraflavescens can Identify the Geographical Origin of Root Samples.2016

    • Author(s)
      Suzuki R, Kai H, Uesawa Y, Matsuno K, Okada Y, Shirataki Y.
    • Journal Title

      Nat Prod Commun.

      Volume: 11 Pages: 73-5

    • NAID

      120005895945

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative Structure-Cytotoxicity Relationship of Oleoylamides.2015

    • Author(s)
      Sakagami H, Uesawa Y, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Takao K, Sugita Y.
    • Journal Title

      Anticancer Res.

      Volume: 35 Pages: 5299-307

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative Structure-Cytotoxicity Relationship of 3-Styryl-2H-chromenes.2015

    • Author(s)
      Uesawa Y, Sakagami H, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Yahagi H, Takao K, Sugita Y.
    • Journal Title

      Anticancer Res.

      Volume: 35 Pages: 5299-307

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Construction of a model for predicting creatinine clearance in Japanese patients treated with Cisplatin therapy.2015

    • Author(s)
      Yajima A, Uesawa Y, Ogawa C, Yatabe M, Kondo N, Saito S, Suzuki Y, Atsuda K, Kagaya H.
    • Journal Title

      Anticancer Res.

      Volume: 35 Pages: 2909-14

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 副作用データベースに基づくオキシコドンの副作用発現傾向の解析2015

    • Author(s)
      永井純子, 植沢芳広, 加賀谷肇
    • Journal Title

      Palliative Care Research

      Volume: 10 Issue: 3 Pages: 161-168

    • DOI

      10.2512/jspm.10.161

    • NAID

      130005093301

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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
    • Journal Title

      薬学雑誌

      Volume: 135 Pages: 969-975

    • NAID

      130005089829

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Warfarin服用患者の出血リスク・INRコントロールに影響を与える要因および出血の季節性に関する検討2015

    • Author(s)
      畠山英司,門田佳子,猿渡 力,大澤友二,加賀谷肇
    • Journal Title

      日本病院薬剤師会雑誌

      Volume: 51 Pages: 297-300

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analyses of opioid-induced adverse effects based on Japanese Adverse Drug Event Report database:Distinctive tendencies of the adverse events induced by morphine, fentanyl and oxycodone2015

    • Author(s)
      永井 純子, 植沢 芳広, 加賀谷 肇
    • Journal Title

      Palliative Care Research

      Volume: 10 Issue: 1 Pages: 113-119

    • DOI

      10.2512/jspm.10.113

    • NAID

      130004943678

    • ISSN
      1880-5302
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 生理的pH条件下の電荷に基づくオピオイドの分布容積の評価2014

    • Author(s)
      植沢芳広,加賀谷肇
    • Journal Title

      日本緩和医療薬学雑誌

      Volume: 7 Pages: 55-61

    • NAID

      40020223868

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Quantitative structure-activity relationship analysis of cytotoxicity and anti- UV activity of 2-aminotropones2014

    • Author(s)
      Sekine S, Shimodaira C, Uesawa Y, Kagaya H, Kanda Y, Ishihara M, Amano O, Sakagami H, Wakabayashi H
    • Journal Title

      Anticancer Res.

      Volume: 34 Pages: 1743-1750

    • NAID

      120005520960

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [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
    • Journal Title

      Anticancer Res.

      Volume: 34 Pages: 4877-4884

    • NAID

      120005520990

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [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
    • Journal Title

      Anticancer Res.

      Volume: 34, Pages: 5405-5411

    • NAID

      120005520991

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Construction of a Prediction Model for Waiting Time of Patients Based on Analyses of Dispensing in a Health Insurance Pharmacy2014

    • Author(s)
      植沢芳広,内田明宏,小山 茜,宇田川三男,武田直子,富澤 崇
    • Journal Title

      Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)

      Volume: 40 Issue: 4 Pages: 215-221

    • DOI

      10.5649/jjphcs.40.215

    • NAID

      130005062829

    • ISSN
      1346-342X, 1882-1499
    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] 今改めて考える、がん疼痛治療におけるオピオイド鎮痛薬の使い方 オキシコドンの体内動態に影響を及ぼす併用薬2014

    • Author(s)
      植沢芳広、加賀谷肇
    • Journal Title

      がん患者と対症療法

      Volume: 25 Pages: 58-64

    • Related Report
      2014 Research-status Report
  • [Journal Article] Evaluation of Cytotoxiciy and Tumor-Specificity of Licorice Flavonoids Based on Chemical Structure2013

    • Author(s)
      Ohno H, Araho D, Uesawa Y, Kagaya H, Ishihara M, Sakagami H, Yamamoto M
    • Journal Title

      Anticancer Research

      Volume: 33 Pages: 3061-3068

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 36 Issue: 1 Pages: 89-95

    • DOI

      10.1248/bpb.b12-00687

    • NAID

      130003361351

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 回復期リハビリテーション病棟と一般病棟の病棟薬剤業務の比較 回復期リハビリテーション病棟業務の特徴2013

    • Author(s)
      藤原久登,濃沼政美,湯本哲郎,前田拓哉,金田昌之,綾部由紀乃,飯田純一,小島昌徳,金田光正,中山はるみ,高尾良洋,齋藤昌久,加賀谷肇,村山純一郎
    • Journal Title

      日本病院薬剤師会雑誌

      Volume: 49 Pages: 975-980

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 機械学習に基づくモルヒネの中枢移行性促進に有用な併用薬の探索2016

    • Author(s)
      植沢 芳広, 福島 大介, 野澤(石井) 玲子, 加賀谷 肇
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tox21 Challenge To Build Predictive Models of Nuclear Receptor and Stress Response Pathways As Mediated by Exposure to Environmental Toxicants and Drugs2016

    • Author(s)
      Uesawa Y
    • Organizer
      The Society of Toxicology 55th Annual Meeting and ToxExpo
    • Place of Presentation
      New Orleans
    • Year and Date
      2016-03-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 米国毒性予測コンペティション“Tox21 DATA Challenge 2014”参加報告2015

    • Author(s)
      植沢芳広
    • Organizer
      CBI学会2015年大会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多職種で終末期を支えるために薬剤師が担うもの2015

    • Author(s)
      加賀谷肇
    • Organizer
      第9回緩和医療薬学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2015-10-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 大規模毒性関連データベースに基づくQSAR予測モデルの構築2015

    • Author(s)
      植沢芳広
    • Organizer
      MOEフォーラム2015
    • Place of Presentation
      東京
    • Year and Date
      2015-07-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 1.Effect of Shitei-To, a traditional Chinese medicine formulation, against hiccups ~Effect of Shitei extract on drug-induced convulsions in mice~2015

    • Author(s)
      Kagaya H, Fukuda E, Baba M, Okada Y, Ishii-Nozawa R
    • Organizer
      14th World Congress of the European Association for Palliative Care
    • Place of Presentation
      Denmark
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 2.Volume of distribution of opioids administered in humans can be estimated by electric charge under biological pH conditions2015

    • Author(s)
      Uesawa Y, Kagaya H
    • Organizer
      14th World Congress of the European Association for Palliative Care
    • Place of Presentation
      Denmark
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 3.Analyses of opioid-induced adverse effects based on PMDA Japanese Adverse Drug Event Report database (JADER) in Japanese patients receiving palliative care2015

    • Author(s)
      Nagai J, Uesawa Y, Kagaya H
    • Organizer
      14th World Congress of the European Association for Palliative Care
    • Place of Presentation
      Denmark
    • Year and Date
      2015-05-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study of concomitant drugs using machine learning QSAR analyses to facilitate brain penetration of morphine2015

    • Author(s)
      Uesawa Y
    • Organizer
      World Congress & Expo on Pharmaceutics & Drug Delivery Systems
    • Place of Presentation
      Dubai
    • Year and Date
      2015-04-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 32.オピオイドの効率的な中枢移行寄与コンパニオンドラッグの探索を指向したトランスポーター制御化合物予測モデルの構築2014

    • Author(s)
      福島大介、植沢芳広、加賀谷 肇
    • Organizer
      第8回日本緩和医療薬学会年会
    • Place of Presentation
      松山
    • Year and Date
      2014-10-03 – 2014-10-05
    • Related Report
      2014 Research-status Report
  • [Presentation] 33.医薬品副作用データベースに基づくオピオイドの副作用発現における性差の解析2014

    • Author(s)
      永井純子、植沢芳広、曽我部直美、加賀谷 肇
    • Organizer
      第8回日本緩和医療薬学会年会
    • Place of Presentation
      松山
    • Year and Date
      2014-10-03 – 2014-10-05
    • Related Report
      2014 Research-status Report
  • [Presentation] ビッグデータを副作用対策に活かす~多変量解析およびデータマイニング手法を用いて副作用を予想する~2014

    • Author(s)
      植沢芳広
    • Organizer
      がんの痛みと症状緩和に関する多施設共同臨床研究会学術大会SCORE-G Summer Seminar in KARUIZAWA
    • Place of Presentation
      軽井沢
    • Year and Date
      2014-08-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 緩和ケアの卒前教育 薬学における緩和ケアの卒前教育の現状と課題2014

    • Author(s)
      加賀谷 肇
    • Organizer
      第19回日本緩和医療学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 14.我が国の医薬品副作用報告に基づくオピオイドの客観的副作用発現頻度解析2014

    • Author(s)
      植沢芳広、加賀谷 肇
    • Organizer
      第19回日本緩和医療学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 化学構造に基づくオピオイド関連化合物の分布容積推定モデルの構築2013

    • Author(s)
      植沢芳広、石井みゆき、加賀谷肇
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] 構造式から推定するオピオイドの体内動態予測 ― 平均残留時間および血漿中半減期について ―2013

    • Author(s)
      植沢芳広、加賀谷 肇
    • Organizer
      第7回日本緩和医療薬学会年会
    • Place of Presentation
      千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] マルチコンパートメントモデルに従う薬物の特徴の解析2013

    • Author(s)
      植沢芳広、加賀谷 肇
    • Organizer
      第23回日本医療薬学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] ラット脳/血漿間非結合形薬物濃度比に基づくヒト脳移行性の推定2013

    • Author(s)
      植沢芳広、加賀谷 肇
    • Organizer
      日本薬物動態学会第28年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Quantitative Structure-pharmacokinetic Relationships (QSPkR) Analysis of Opioids2013

    • Author(s)
      Yoshihiro Uesawa, Miyuki Ishii, Hajime Kagaya
    • Organizer
      CBI学会2013年大会 -生命医薬情報学連合大会-
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 緩和薬物療法の新たな潮流を考える2013

    • Author(s)
      加賀谷 肇
    • Organizer
      第18回日本緩和医療学会学術大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 日本緩和医療薬学会の紹介とオピオイドの使い方2013

    • Author(s)
      加賀谷 肇
    • Organizer
      第46回日本薬剤師会学術大会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 緩和医療薬学-SCIENCEとARTの融合と実践-2016

    • Author(s)
      加賀谷肇、植沢芳広、野澤玲子
    • Total Pages
      192
    • Publisher
      京都廣川(2016)
    • Related Report
      2015 Annual Research Report
  • [Book] トワイクロス先生のがん緩和ケア処方薬2013

    • Author(s)
      加賀谷肇(分担翻訳)
    • Total Pages
      3
    • Publisher
      医学書院
    • Related Report
      2013 Research-status Report
  • [Book] WHOガイドライン 病態に起因した小児の持続性の痛みの薬による治療2013

    • Author(s)
      加賀谷肇(分担翻訳)
    • Total Pages
      13
    • Publisher
      金原出版
    • Related Report
      2013 Research-status Report
  • [Book] 緩和ケアチーム 活動の手引き 第2版2013

    • Author(s)
      加賀谷肇(分担執筆)
    • Total Pages
      3
    • Publisher
      日本緩和医療学会
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi