| Project/Area Number |
17K11924
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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 |
Surgical dentistry
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| Research Institution | Asahi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
溝上 真樹 福井大学, 学術研究院医学系部門, 特別研究員 (10231614)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 麻酔薬 / 薬理学的多様性 / キラル / 生体膜 / 膜脂質二重層 / コレステロール / 機序的膜相互作用 / 立体特異性 / 相互作用 / 薬物識別 / 異性体識別 |
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| Outline of Final Research Achievements |
General and local anesthetics possess various activities other than the intrinsic anesthetic activity and their relative potencies significantly differ by drug structures. However, such stereospecific pharmacological diversity cannot be interpreted by the conventional drug action on receptors and ion channels. Therefore, we focused on the ability of biomembranes to discriminate slightly different chemical structures and investigated the interactions of drugs with model biomembranes by a series of experiments. With respect to the membrane interactivity, we discussed importance as mechanistic background and clinical significance.
Consequently, we found that anesthetics and anesthetic adjuncts interact with chiral cholesterol-containing phospholipid membranes to modify their fluidity depending on drug stereostructures. We also tried to construct the pharmacological theory that the membrane interaction mechanism would be applied to analgesics, anti-inflammatory drugs and others.
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| Academic Significance and Societal Importance of the Research Achievements |
全身麻酔薬、局所麻酔薬ならびに麻酔補助薬が有する本来の臨床効果に加えて抗酸化、抗菌、抗血小板、抗腫瘍などの様々な活性に関し、新規の薬理学的作用機序を提唱することができた。したがって、本研究成果に基づき、従来とは異なる機序的視点から、麻酔薬だけでなく麻酔関連薬の有用・有害作用を考察・予測できるとともに、多様な薬理活性の有効利用により適した薬物を選択できる可能性もある。さらに、機序的膜相互作用の構想は、麻酔薬以外の薬物にも広く拡張できると期待される。
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