Elucidation of molecular pharmacological profile of mu opioid receptor agonists, and clinical applications thereof

Research Project

Project/Area Number	17K11105
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	University of Toyama
Principal Investigator	Yamazaki Mitsuaki 富山大学, 学術研究部医学系, 教授 (70158145)
Co-Investigator(Kenkyū-buntansha)	成田年星薬科大学, 薬学部, 教授 (40318613)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	μオピオイド受容体作動薬 / TRV130 / βアレスチン / 薬理学的プロファイル / オピオイド鎮痛薬 / Ligand-biased efficacy / cAMP / β-arrestin / μオピオイド受容体
Outline of Final Research Achievements	Increasing action of β-arrestin recruitment with fentanyl and methadone was increased by combination of loperamide and oxycodone. On the other hand, β-arrestin recruitment increasing action by fentanyl was remarkably decreased by hydromorphone together with fentanyl. After calculating the side effect coefficient based on constipation and painkilling strength of each strong opioid, and then analyzing the correlation of the bias coefficient by each strong opioid, no significant differences were observed between these coefficients. After performing comparison between morphine and TRV130 about painkilling, constipation, vomiting, nausea and spontaneous momentum, big differences were not recognized between two drugs.
Academic Significance and Societal Importance of the Research Achievements	本研究では、オピオイド受容体作動薬の薬理学的プロファイルを検討した。この研究成果から、オピオイド製剤の適正使用の理解が深まり、オピオイド使用に関するアルゴリズムの確立に寄与できたものと思われる。そして、オピオイドの適正使用や効率的なオピオイドスイッチングに有用な情報を与える事が出来るものと考える。