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Drug-Selection Standard for Multimodal Analgesia Using Mechanistic Membrane Interactivity Specific to Each Applicable Drug

Research Project

Project/Area Number 20K10152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionAsahi University

Principal Investigator

Tsuchiya Hironori  朝日大学, その他部局等, 名誉教授 (30131113)

Co-Investigator(Kenkyū-buntansha) 溝上 真樹  社会医療法人厚生会中部国際医療センター(研究支援センター), がん研究部, 研究員 (10231614)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsマルチモーダル鎮痛 / 適用薬 / 機序的膜相互作用 / 生体膜 / 膜流動性変化 / 薬物選択基準 / COVID-19 / 非ステロイド系抗炎症薬 / NSAIDs / 機序的生体膜相互作用 / アセトアミノフェン / カプサイシン / COVID-19罹患後口腔症状 / COVID-19口腔症状 / SARS-CoV-2感染 / 特異的
Outline of Research at the Start

アセトアミノフェン、NSAIDs(イブプロフェン、他)、選択的COX2阻害薬(コキシブ系)、α2-アゴニスト(デクスメデトミジン)、長時間作用型局所麻酔薬(ブピバカイン)、静脈内投与局所麻酔薬(リドカイン)、NMDA受容体アンタゴニスト(ケタミン)、TRPV1アゴニスト(カプサイシン)、GABA誘導体抗てんかん薬(ガバペンチン、他)、SNRI(デュロキセチン)などのマルチモーダル鎮痛適用薬について、疑似生体膜(リポソーム)との相互作用を蛍光偏光法で解析する。一連の実験から得られる各薬物の機序的膜相互作用に関する基礎的知見に基づき、マルチモーダル鎮痛の薬物選択基準としての可能性を追究する。

Outline of Final Research Achievements

We studied the membrane interactions of diverse drugs applied to multimodal analgesia in order to gain a new insight into their mechanisms and use the drug structure-specific membrane activity as one of criteria for drug selection. During the COVID-19 pandemic, we could not conduct originally planned experiments and research presentations, therefore, entirely focused on the preliminary experiments for performing a series of studies. Based on their results, we analyzed the biomimetic membrane interactions of acetaminophen in 2021, capsaicin in 2022, and nonsteroidal anti-inflammatory drugs in 2023 by using a fluorescence polarization method. Consequently, we found the possibility that the membrane interactivity is a property common to drugs used in multimodal analgesia and also characterized them based on the membrane interaction-induced changes in membrane fluidity.

Academic Significance and Societal Importance of the Research Achievements

鎮痛効果を高めるとともに副作用を軽減するために薬物を併用したマルチモーダル鎮痛が、疼痛管理や術後鎮痛に注目されている。しかし、適用薬に対し、科学的根拠に基づく選択法は確立されていない。そこで、薬物選択基準としての利用を目指し、新規作用機序を追究した。生体膜モデル実験から、マルチモーダル鎮痛に現在用いられている全薬物が膜相互作用を示すことを見出した。代表薬:アセトアミノフェン、カプサイシン、非ステロイド系抗炎症薬を比較し、各薬物の膜活性を特徴づけることができた。
コロナ禍の期間、本研究コンセプトがCOVID-19の治療にも応用できる可能性から、COVID-19に関する総説研究へと発展した。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021 2020

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (5 results)

  • [Journal Article] COVID-19 in Dental Practice Is Prevented by Eugenol Responsible for the Ambient Odor Specific to Dental Offices: Possibility and Speculation2024

    • Author(s)
      Tsuchiya Hironori、Takai Yoshiaki
    • Journal Title

      Medical Principles and Practice

      Volume: 33 Issue: 2 Pages: 1-7

    • DOI

      10.1159/000535966

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Oral Cavity Potentially Serving as a Reservoir for SARS-CoV-2 but Not Necessarily Facilitating the Spread of COVID-19 in Dental Practice2023

    • Author(s)
      Tsuchiya Hironori
    • Journal Title

      European Journal of Dentistry

      Volume: 17 Issue: 02 Pages: 310-318

    • DOI

      10.1055/s-0042-1757909

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] COVID-19 Oral Sequelae: Persistent Gustatory and Saliva Secretory Dysfunctions after Recovery from COVID-192023

    • Author(s)
      Tsuchiya Hironori
    • Journal Title

      Medical Principles and Practice

      Volume: 32 Issue: 3 Pages: 166-177

    • DOI

      10.1159/000531373

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatments of COVID-19-Associated Taste and Saliva Secretory Disorders2023

    • Author(s)
      Tsuchiya Hironori
    • Journal Title

      Dentistry Journal

      Volume: 11 Issue: 6 Pages: 140-140

    • DOI

      10.3390/dj11060140

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane Interactivity of Capsaicin Antagonized by Capsazepine2022

    • Author(s)
      Maki Mizogami and Hironori Tsuchiya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 7 Pages: 3971-3971

    • DOI

      10.3390/ijms23073971

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity2022

    • Author(s)
      Maki Mizogami and Hironori Tsuchiya
    • Journal Title

      Medical Principles and Practice

      Volume: 31 Issue: 2 Pages: 111-117

    • DOI

      10.1159/000524210

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gustatory and Saliva Secretory Dysfunctions in COVID-19 Patients with Zinc Deficiency2022

    • Author(s)
      Hironori Tsuchiya
    • Journal Title

      Life

      Volume: 12 Issue: 3 Pages: 353-353

    • DOI

      10.3390/life12030353

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review2021

    • Author(s)
      Hironori Tsuchiya
    • Journal Title

      Dentistry Journal

      Volume: 9(3) Issue: 3 Pages: 32-32

    • DOI

      10.3390/dj9030032

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization and Pathogenic Speculation of Xerostomia Associated with COVID-19: A Narrative Review2021

    • Author(s)
      Hironori Tsuchiya
    • Journal Title

      Dentistry Journal

      Volume: 9(11) Issue: 11 Pages: 130-130

    • DOI

      10.3390/dj9110130

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent Gustatory Dysfunction in COVID-19 Survivors: A Narrative Literature Review2021

    • Author(s)
      Hironori Tsuchiya
    • Journal Title

      Journal of Advances in Medicine and Medical Research

      Volume: 33(22) Pages: 94-119

    • DOI

      10.9734/jammr/2021/v33i2231162

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interaction of drugs with lipid raft membrane domains as a possible target2020

    • Author(s)
      Hironori Tsuchiya, Maki Mizogami
    • Journal Title

      Drug Target Insights

      Volume: 14 Issue: 1 Pages: 34-47

    • DOI

      10.33393/dti.2020.2185

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マルチモーダル鎮痛に用いられる薬物の膜相互作用(Ⅵ):COX-2選択性が異なるNSAIDsの機序的な生体膜相互作用の比較2023

    • Author(s)
      溝上真樹、土屋博紀
    • Organizer
      日本麻酔科学会第70回学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マルチモーダル鎮痛に用いられる薬物の膜相互作用(Ⅴ):カプサイシンの濃度依存性膜作用とTRPV-1アンタゴニストのカプサゼピンによる競合的拮抗2022

    • Author(s)
      溝上真樹、土屋博紀
    • Organizer
      日本麻酔科学会第69回学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 非ステロイド系抗炎症薬(NSAIDs)は生体膜と相互作用して構造特異的に膜流動性を修飾する2022

    • Author(s)
      溝上真樹、飯田宏樹、重見研司、土屋博紀
    • Organizer
      第44回日本疼痛学会
    • Related Report
      2022 Research-status Report
  • [Presentation] マルチモーダル鎮痛に用いられる薬物の膜相互作用(Ⅳ):アセトアミノフェンとフェナセチンの有用・有害作用に関する比較2021

    • Author(s)
      溝上真樹、土屋博紀、山田宏和、越川桂、畑中奈津実、和泉有希乃
    • Organizer
      日本麻酔科学会第68回学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] マルチモーダル鎮痛に用いられる薬物の膜相互作用(Ⅲ)アセトアミノフェンの機序的膜相互作用2020

    • Author(s)
      溝上真樹、土屋博紀、山田宏和、越川桂、竹中志穂
    • Organizer
      日本麻酔科学会第67回学術集会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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