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A novel pharmacodynamic approach to assess individual differences in anesthetic response: The function of lipids in biological membrane

Research Project

Project/Area Number 16K10931
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionUniversity of Fukui

Principal Investigator

Mizogami Maki  福井大学, 学術研究院医学系部門, 特別研究員 (10231614)

Co-Investigator(Kenkyū-buntansha) 土屋 博紀  朝日大学, その他部局等, 名誉教授 (30131113)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords麻酔薬 / 生体膜相互作用 / 個人差 / 麻酔学
Outline of Final Research Achievements

Pharmacological diversity of anesthetics cannot be fully explained by only the direct action on ion channel and receptor. In the light of a novel mechanistic interaction with biomembrane lipid bilayers, we verify the possible relation between individual differences in anesthetic response and lifestyle diseases such as aging, diet, diabetes and cancer, all of which would modify or alter the lipid composition and function of membranes.
Consequently, we found that all the tested anesthetics acted on biomembranes and the relative potencies of membrane action correlated with those of various pharmacological activities. It was experimentally proved that the increase of cholesterol in cell membrane, induced by dietary habits or lifestyle diseases, influenced the chiral activity of anesthetics. We also investigated the structure-specific membrane interactivity of antipyretic analgesics and other drugs which has been the focus of attention in recent years.

Academic Significance and Societal Importance of the Research Achievements

薬物の機序的膜相互作用という視点から、後天的な要因によって変化する生体膜脂質組成を同定し、高齢化や生活習慣病が薬物の麻酔作用自体に及ぼす影響ついて新しい知見を得ることができた。その結果として、従来の患者の体重や年齢だけでなく、生活習慣病合併の有無を加味した麻酔薬の適量を各麻酔患者に設定できれば、まさにテーラーメイド型の麻酔管理という課題に対して基礎研究から応えることになる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017 2016

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (13 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Membrane interactivity of anesthetic adjuvant dexmedetomidine discriminable from clonidine and enantiomeric levomedetomidine.2019

    • Author(s)
      Mizogami M, Tsuchiya H
    • Journal Title

      Journal of Advances in Medicine and Medical Research

      Volume: 29(11) Pages: 1-15

    • DOI

      10.9734/jammr/2019/v29i1130142

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane Interactivity of Non-steroidal Anti-inflammatory Drugs: A Literature Review2019

    • Author(s)
      Tsuchiya H, Mizogami M
    • Journal Title

      Journal of Advances in Medicine and Medical Research

      Volume: 31(9) Pages: 1-30

    • DOI

      10.9734/jammr/2019/v31i930320

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sudden cardiac arrest due to coronary vasospasm in a patient with Wolff-Parkinson-White syndrome during brain surgery: a case report.2019

    • Author(s)
      Matsuki Y, Mizogami M and Shigemi K
    • Journal Title

      JA Clinical Reports

      Volume: 5 Issue: 1 Pages: 13-13

    • DOI

      10.1186/s40981-019-0233-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Herbs affect anesthesia by the pharmacokinetic and pharmacodynamic interactions of herbal phytochemical components with anesthetic agents.2018

    • Author(s)
      Tsuchiya H, Mizogami M
    • Journal Title

      Reviews and Reports Press

      Volume: 2(1) Pages: 44-54

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain.2018

    • Author(s)
      Matsuki Y, Sukenaga N, Miyagi K, Tsunetoh T, Mizogami M, Shigem K, Maeda L, Hirose M
    • Journal Title

      Journal of Anesthesia

      Volume: 32(3) Issue: 3 Pages: 403-408

    • DOI

      10.1007/s00540-018-2495-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrimination of Stereoisomers by Their Enantioselective Interactions with Chiral Cholesterol-Containing Membranes.2017

    • Author(s)
      Tsuchiya H, Mizogami M
    • Journal Title

      Molecules

      Volume: 23(1) Issue: 1 Pages: 49-49

    • DOI

      10.3390/molecules23010049

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A randomized controlled trial to verify the efficacy of alkalinized local anesthetics in ultrasound-guided supraclavicular brachial plexus block.2017

    • Author(s)
      Tsugita K, Matsuki Y, Murakami T, Mizogami M, Shigemi K.
    • Journal Title

      Anaesthesia, Pain & Intensive Care

      Volume: 21(3) Pages: 301-305

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Medicinal Chemistry of Non-Steroidal Anti-Inflammatory and Antipyretic Drugs: Characterization of Their Interactivity with Lipid Bilayer Membranes.2020

    • Author(s)
      Mizogami M, Tsuchiya H
    • Organizer
      International Congress on Natural Sciences and Engineering (2020 ICNSE)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マルチモーダル鎮痛に用いられる薬物の膜相互作用(Ⅱ): 多様な適応薬が共有する膜流動性修飾用2019

    • Author(s)
      溝上真樹、土屋博紀、畑中奈津実、越川 桂、山田宏和
    • Organizer
      日本麻酔科学会第66回学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Membrane Interactivity Shared by Different Drugs That Act on Membrane-Associated Receptor, Ion Channel and Enzyme: A Tool for Screening Lead Compounds.2019

    • Author(s)
      Tsuchiya H, Mizogami M
    • Organizer
      18th Edition of International Conference and Exhibition on Pharmaceutics and Novel Drug Delivery Systems
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study in medicinal chemistry of receptor-acting drugs: their membrane interactivity specific to chemical structures.2019

    • Author(s)
      Tsuchiya H, Mizogami M
    • Organizer
      International Congress on Natural Sciences and Engineering (2019 ICNSE)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] マルチモーダル鎮痛に用いられる種々の薬物に関する機序的膜作用の特徴2018

    • Author(s)
      溝上真樹、土屋博紀、竹内健二、神澤聖一、佐上祐介、重見研司
    • Organizer
      日本麻酔科学会第65回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Structure-specific membrane action of phytochemicals responsible for their bioactivities.2018

    • Author(s)
      Tsuchiya H, Mizogami M, Shigemi K
    • Organizer
      International Symposium on Engineering and Applied Science (2018 ISEAS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] デクスメデトミジンの機序的膜作用(Ⅲ):立体異性体の識別に関与する特異的膜部位と膜ステロール構造2017

    • Author(s)
      溝上真樹、早渕光代、早渕由朗、重見研司、土屋博紀
    • Organizer
      日本麻酔科学会第64回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Differentiation of drug stereoisomers by their stereostructure-selective membrane interactions as one of pharmacological mechanisms2017

    • Author(s)
      Mizogami M, Tsuchiya H, Hayabuchi Y, Shigem K.
    • Organizer
      19th International Conference on Pharmacology, Medicinal and Pharmaceutical Sciences (ICPMPS 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stereospecific Effects of Cholesterol on Membrane Property and Drug Action2017

    • Author(s)
      Tsuchiya H, Mizogami M, Shigem K.
    • Organizer
      International Biotechnology, Chemical Engineering and Life Science Conference (2017 IBCELC)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] デクスメデトミジンの機序的膜作用(Ⅱ):脂質組成に依存して立体異性体間で識別できる膜相互作用2016

    • Author(s)
      溝上真樹、松木悠佳、重見研司、土屋博紀
    • Organizer
      日本麻酔科学会第63回学術集会
    • Place of Presentation
      マリンメッッセ(福岡市)
    • Related Report
      2016 Research-status Report
  • [Presentation] Differentiation of enantiomers for drug design: enantioselective interactions of drugs with chiral membranes as their pharmacological target2016

    • Author(s)
      Tsuchiya H, Mizogami M
    • Organizer
      10th Drug Design and Medicinal Chemistry Conference
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Interaction of anesthetic agents with neuro-active indoleamine-aldehyde condensation products.2016

    • Author(s)
      Tsuchiya H, Mizogami M
    • Organizer
      3rd International Biotechnology, Chemical Engineering and Life Science Conference (IBCELC)
    • Place of Presentation
      Okinawa, Japan
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enantiomers of anesthetic agent are discriminated by their interactivity with chiral lipid.2016

    • Author(s)
      Mizogami M, Tsuchiya H, Shigemi K
    • Organizer
      16th World Congress of Anaesthesiologists (WCA)
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2021-02-19  

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