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

The interaction between Mammalian Alkaloids and Anesthetics : Anesthetic Tolerance Associated with Alcohol Drinking and Prediction by Hair Analysis

Research Project

Project/Area Number15592145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionAsahi University

Principal Investigator

TSUCHIYA Hironori  Asahi University, School of Dentistry, Professor, 歯学部, 教授 (30131113)

Co-Investigator(Kenkyū-buntansha) MIZOGAMI Maki  Asahi University, School of Dentistry, Associate Professor, 歯学部, 助教授 (10231614)
NAGAYAMA Motohiko  Asahi University, School of Dentistry, Lecturer, 歯学部, 講師 (50298436)
Project Period (FY) 2003 – 2005
Project Status Completed(Fiscal Year 2005)
Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 2005 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2004 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 2003 : ¥1,300,000 (Direct Cost : ¥1,300,000)
KeywordsAnesthetics / Drinking / Decreased Effects / Interaction / Beta-carbolines / Membrane Fluidization / Hair Analysis / Pharmacological Mechanism / β-カルボリンアルカロイド / 膜流動性 / 生体膜マイクロドメイン / 立体異性体 / コレステロール / 生体膜流動性 / リポソーム / 麻酔効果減弱 / 膜流動性変化 / 局所・全身麻酔薬 / 哺乳類アルカロイド
Research Abstract

Concerning anesthetic tolerance associated with drinking, the pharmacological background and prediction method were studied with focusing on the interaction with mammalian alkaloidal β-carbolines. A series of results were applied to various investigations on anesthetic effect change and biomembrane-drug interaction.
1.Certain β-carbolines acted on membrane lipids to inhibit the membrane fluidization by local and general anesthetics. Such inhibition disappeared by their hepatic hydroxylation metabolism. It is speculated that anesthetic effects are decreased by the interaction with membrane-active β-carbolines increased in vivo by drinking.
2.In the newly developed HPLC, the β-carboline concentrations in human scalp hair were found to significantly increase in chronic alcoholics. The potent interaction with β-carbolines to influence anesthesia may be predicted by hair analysis.
3.Local anesthetics showed the reversed-phase chromatographic retention and membrane-fluidizing activity relations … More hips. Based on the hydrophobic interaction underlying membrane fluidization, the changes in anesthetic effects are simulated by HPLC analysis.
4.The hydrophobic interaction of local anesthetics was applied to infusion balloons, which adsorbed local anesthetics immediately after injection to decrease their concentrations in effluents. Attention should be given to such adsorption so as not to influence clinical effects.
5.The membrane-fluidizing effects of local anesthetics were induced under inflammatory acidic conditions and inhibited by inflammatory peroxynitrite, conflicting with the conventional hypothesis. The alternative mechanism should be theorized for the anesthetic failure in inflamed tissues.
6.Nerve cell model membranes were fluidized by lidocaine ionic quaternary ammonium derivative and stereostructure-specifically fluidized by S(-)-,R(+)- and racemic bupivacaine and ropivacaine. The interaction with membrane lipids is responsible for the effects of local anesthetics in addition to that with ion channel/receptor proteins.
7.Anesthetic-relating drugs, including new selective β-blockers and phenolic agents, showed the structure-selective membrane-activity, suggesting that the modification of membrane fluidity mechanistically contributes to their effects. Less

Report

(4results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report

Research Products

(19results)

All 2005 2004 2003 Other

All Journal Article Publications

  • [Journal Article] Reversed-phase liquid chromatographic retention and membrane activity relationships of local anesthetics2005

    • Author(s)
      Hironori Tsuchiya, et al.
    • Journal Title

      Journal of Chromatography A 1073

      Pages : 303-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comparative Membrane-Fluidizing Effects of Phenolic Agents2005

    • Author(s)
      Hironori Tsuchiya, et al.
    • Journal Title

      Dentistry in Japan 41

      Pages : 35-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Interaction of Local Anesthetic Quaternary Ammonium Derivative and Stereoisomers with Membrane Lipids2005

    • Author(s)
      Hironori Tsuchiya, et al.
    • Journal Title

      Journal of the Pharmaceutical Society of Japan 125(Suppl.4)

      Pages : 148-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reversed-phase liquid chromatographic retention and membrane activity relationships of local anesthetics2005

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

      Journal of Chromatography A 1073

      Pages : 303-308

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Interaction of Local Anesthetic Quaternary Ammonium Derivative and Stereoisomers with Membrane Lipids2005

    • Author(s)
      Hironori Tsuchiya, Maki Mizogami, Masanori Kashimata, Ko Takakura
    • Journal Title

      Journal of the Pharmaceutical Society of Japan 125・Suppl.4

      Pages : 148-149

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reversed-phase liquid chromatographic retention and membrane activity relationships of local anesthetics2005

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

      Journal of Chromatography A (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High-performance liquid chromatographic analysis of β-carbolines in human scalp hair2004

    • Author(s)
      Hironori Tsuchiya
    • Journal Title

      Journal of Chromatography A 1031

      Pages : 325-330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Local Anesthetics Adsorbed onto Infusion Balloon2004

    • Author(s)
      Maki Mizogami, et al.
    • Journal Title

      Anesthesia and Analgesia 99

      Pages : 764-768

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 新規β_1選択的遮断藥の膜作用の可能性2004

    • Author(s)
      大嶋和之, 他
    • Journal Title

      薬学雑誌 124(Suppl.4)

      Pages : 129-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 構造ならびに液性に依存した局所麻酔薬の膜流動化作用と逆相分配HPLC保持能2004

    • Author(s)
      土屋博紀, 他
    • Journal Title

      薬学雑誌 124(Suppl.4)

      Pages : 133-136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potent Membrane Effects of New Selective β_1-Blockers2004

    • Author(s)
      Kazuyuki Ooshima, et al.
    • Journal Title

      Journal of the Pharmaceutical Society of Japan 124(Suppl.4)

      Pages : 129-132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure- and pH-Dependent Membrane-Fluidizing Effects and Reversed-Phase Partition HPLC Retention Characteristics of Local Anesthetics2004

    • Author(s)
      Hironori Tsuchiya, et al.
    • Journal Title

      Journal of the Pharmaceutical Society of Japan 124(Suppl.4)

      Pages : 133-136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Local Anesthetics Adsorbed onto Infusion Balloon2004

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

      Anesthesia and Analgesia 99

      Pages : 764-768

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 新規β1選択的遮断薬の膜作用の可能性2004

    • Author(s)
      大嶋和之, 溝上真樹, 土屋博紀, 永山元彦, 高倉康
    • Journal Title

      薬学雑誌 124・Suppl.4

      Pages : 129-132

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 構造ならびに液性に依存した局所麻酔薬の膜流動化作用と逆相分配HPLC保持能2004

    • Author(s)
      土屋博紀, 溝上真樹, 大嶋和之, 柏俣正典, 高倉康
    • Journal Title

      薬学雑誌 124・Suppl.4

      Pages : 133-136

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 炎症組織における局所麻酔効果減弱の仮説的機序-局所麻酔薬の膜流動化作用に及ぼすpHとPeroxynitriteの影響-2003

    • Author(s)
      溝上真樹, 他
    • Journal Title

      薬学雑誌 123(Suppl.4)

      Pages : 201-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypothetic Mechanism for Decreased Local Anesthetic Effects in Inflamed Tissues Influences of pH and Peroxynitrite on Membrane Fluidization by Local Anesthetics-2003

    • Author(s)
      Maki MIZOGAMI, et al.
    • Journal Title

      Journal of the Pharmaceutical Society of Japan 123(Suppl.4)

      Pages : 201-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] 溝上真樹, 土屋博紀, 永山元彦, 他: "炎症組織における局所麻酔効果減弱の仮説的機序 -局所麻酔薬の膜流動化作用に及ぼすpHとPeroxynitriteの影響-"薬学雑誌. 123・Suppl.4. 201-204 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hironori Tsuchiya: "High-performance liquid chromatographic analysis of β-carbolines in human scalp hair"Journal of Chromatography A. in press. (2004)

    • Related Report
      2003 Annual Research Report

URL :

Published : 2003-04-01   Modified : 2016-04-21  

Information FAQ News Terms of Use

Powered by NII kakenhi