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Membrane Interaction of Analgesic Agents as Their Mode of Action: A Possible Clue to Discover Drug Leads
https://asahi-u.repo.nii.ac.jp/records/7263
https://asahi-u.repo.nii.ac.jp/records/7263345344ae-811f-4cc3-b010-c58670ecc393
| Item type | 朝日大学 教育・研究業績(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-10-12 | |||||
| タイトル | ||||||
| タイトル | Membrane Interaction of Analgesic Agents as Their Mode of Action: A Possible Clue to Discover Drug Leads | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_1843 | |||||
| 資源タイプ | other | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 業績分類 | ||||||
| 値 | 学会発表 | |||||
| 教員氏名 |
土屋, 博紀
× 土屋, 博紀 |
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| 発行、発表雑誌等、又は発表学会等の名称 | ||||||
| 値 | The 3rd International Scientific Conference on Engineering and Applied Sciences ISCEAS 2015 (Naha, Okinawa) | |||||
| 単著、共著の別 | ||||||
| 値 | 共同発表 | |||||
| 発行又は発表の年月 | ||||||
| 日付 | 2015-07-29 | |||||
| 概要 | ||||||
| 値 | Objective: Various drugs used for pain relief possess diverse pharmacological properties besides their intrinsic analgesic activity. In order to verify the underlying mode of action, we studied the effects of selected analgesic agents on lipid bilayer membranes to induce the physicochemical changes in common, but structure-specifically. Methods: Biomimetic membranes were prepared with different phospholipids and cholesterol to be unilamellar vesicles, which were treated with local anesthetic lidocaine, bupivacaine and ropivacaine; phenolic sedative/anesthetic thymol, eugenol, guaiacol and propofol; non-steroidal anti-inflammatory ibuprofen and indomethacin; N-methyl-D-aspartate receptor antagonistic ketamine; and their stereoisomers at pharmacologically-relevant concentrations. Drugs-induced changes in membrane fluidity were determined by measuring fluorescence polarization. Results: All the tested drugs interacted with biomimetic membranes to modify their fluidity. Lidocaine, bupivacaine, ropivacaine, thymol, eugenol, guaiacol, propofol and ketamine structure-dependently increased the membrane fluidity at 0.1–200 μM, whereas ibuprofen and indomethacin decreased the membrane fluidity at 100–200 μM. In the membranes consisting of 35–45 mol% chiral cholesterol, stereoisomers (25–200 μM) produced the stereospecific membrane interactions with the relative potencies being R(+)-bupivacaine > racemic bupivacaine > S(–)-bupivacaine, S(+)-ketamine > racemic ketamine, and S(+)-ibuprofen > racemic ibuprofen > R(–)-ibuprofen, correlating to those of their analgesic, anesthetic and cardiotoxic effects. Conclusion: Analgesic agents share the ability to interact with lipid bilayers, directly influencing the functions of biomembranes and indirectly modulating the activities of membrane-associated proteins through the conformational alterations. Their pharmacological diversity would be accounted for by the mechanistic membrane interaction, which may also be a possible clue to discover drug leads with the analgesic potential. | |||||
