Antinociceptive and side effects of novel oral active indole alkaloids

• Project/Area Number: 20790075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Josai International University
• Principal Investigator: MATSUMOTO Kenjiro Josai International University, 薬学部, 助手 (10406770)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: オピオイド / インドールアルカロイド / モルヒネ / ミトラガイニン / 痛み / 経口活性 / オピオイド受容体 / Mitragynine / 抗侵害作用 / μオピオイド受容体 / δオピオイド受容体

Research Abstract

本研究ではインドール骨格を基本骨格とする7-hydroxymitragynine(7-OHMG)関連化合物の鎮痛活性の評価、副作用の検討、作用機序解析を行った。我々の検討により、強力な鎮痛活性と低い副作用特性を合わせ持つMGM-9やモルヒネより約45倍強力な鎮痛活性を有する化合物MGM-16等が発見された。またMitragynine関連化合物について国内、米国、国際特許出願を行った。

Research Products

• [Journal Article] Neurogenic contraction of mouse rectum via the cyclooxygenase pathway : Changes of PGE2-induced contraction with dextran sulfate sodium-induced colitis. (2010)
  • Author(s): Hamada, Y
  • Journal Title: Pharmacological Research 61 Pages: 48-57
  • Peer Reviewed
• [Journal Article] Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon American Journal of Physiology (2009)
  • Author(s): 松本健次郎, 他7名
  • Journal Title: Gastrointestinal and Liver Physiology 54
  • Peer Reviewed
• [Journal Article] Subdiaphragmatic vagotomy promotes nociceptive sensitivity of deep tissue in rats. (2009)
  • Author(s): Furuta, S
  • Journal Title: Neuroscience 164 Pages: 1252-1262
  • Peer Reviewed
• [Journal Article] Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine : high abundance and sensitivity in rectum and distal colon. (2009)
  • Author(s): Matsumoto, K
  • Journal Title: American Journal of Physiology, Gastrointestinal and Liver Physiology 297
  • Peer Reviewed
• [Journal Article] MGM-9 [(E)-methyl 2-(3-ethyl-7a,12a-(epoxyethanoxy)-9-fluoro-1,2,3,4,6,7,12,12b-octahydro-8-methoxyindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate], a derivative of the indole alkaloid mitragynine: a novel dual-acting mu- and kappa-opioid agonist with potent antinociceptive and weak rewarding effects in mice (2008)
  • Author(s): 松本健次郎, 他11名
  • Journal Title: Neuropharmacology 54 Pages: 154-165
  • Peer Reviewed
• [Journal Article] Validation of 13C-acetic acid breath test by measuring effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice (2008)
  • Author(s): Matsumoto, K.
  • Journal Title: Biological and Pharmaceutical and Bulletin 31 Pages: 1917-1922
  • NAID: 110006936334
  • Peer Reviewed
• [Journal Article] Chemical constituents of Aristolochia constricta : antispasmodic effects of its constituents in guinea-Dig ileum and isolation of a diterneno-lienan hybrid (2008)
  • Author(s): Zhang, G.
  • Journal Title: Journal of Natural Product 71 Pages: 1167-1172
  • Peer Reviewed
• [Journal Article] MGM-9[(E)-methyl 2-(3-ethyl-7a, 12a-(epoxyethanoxy)-9-fluoro-1, 2, 3, 4, 6, 7, 12, 12b-octahydro-8- methoxyindolo[2, 3-a]quinolizin-2-y1) -3-methoxyacrylatel, a derivative of the indole alkaloid mitragynine : a novel dual-acting mu- and kappa-opioid agonist with potent antinociceptive and weak rewarding effects in (2008)
  • Author(s): Matsumoto, K.
  • Journal Title: Neuropharmacology 54 Pages: 154-165
  • Peer Reviewed
• [Journal Article] 温度と辛味を感じる受容体-消化管にとってよい受容体か?悪い受容体か (2008)
  • Author(s): 堀江俊治
  • Journal Title: G.I. Research 16 Pages: 403-410
• [Presentation] マウス下部消化管におけるTRPV1発現神経の分布と神経ペプチド,セロトニン,NO合成酵素の局在に関する免疫組織学的検討 (2010)
  • Author(s): 松本健次郎
  • Organizer: 第6回日本消化管学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-02-20
• [Presentation] マウス下部消化管におけるTRPV1発現神経と神経ペプチドとの局在に関する免疫組織学的検討 (2009)
  • Author(s): 松本健次郎
  • Organizer: 第11回日本神経消化器病学会
  • Place of Presentation: 仙台
  • Year and Date: 2009-09-25
• [Presentation] マウス下部消化管におけるTRPV1発現神経と神経ペプチドとの局在に関する免疫組織学的検討 (2009)
  • Author(s): 松本健次郎
  • Organizer: 日本神経消化器病学会
  • Place of Presentation: 仙台
  • Year and Date: 2009-09-21
• [Presentation] Immunohistochemical characterization of transient receptor potential vanilloid (TRPV) 1 and sensory neuropeptides in mouse rectum : clear differences of the subpopulations in mucosal, submucosal and muscle layer (2009)
  • Author(s): 松本健次郎
  • Organizer: Digestive Disease Week and the 109th Annual Meeting of the American Gastroenterological Association Institute
  • Place of Presentation: 米国・シカゴ
  • Year and Date: 2009-06-02
• [Presentation] マウス直腸におけるTRPV1発現神経と神経ペプチドの局在に関する免疫組織学的検討 (2009)
  • Author(s): 松本健次郎
  • Organizer: 日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-16
• [Presentation] マウス摘出下部消化管におけるバニロイド受容体TRPV1の局在とカプサイシン誘起平滑筋収縮作用機序の解明 (2008)
  • Author(s): 松本健次郎
  • Organizer: 生体機能と創薬シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-09-05
• [Presentation] Differences in localization of TRPV1 channels and contractile effect of capsaicin in mouse isolated lower gastrointestinal tract: higher abundance and sensitivity of TRPV1 channels in rectum and distal colon than in transverse and proximal colon (2008)
  • Author(s): 松本健次郎
  • Organizer: Digestive Disease Week and the 109th Annual Meeting of the American Gastroenterological Association Institute
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-05-21
• [Presentation] Differences in localization of TRPV1 channels and contractile effect of capsaicin in mouse isolated lower gaRtrointestinal trant7 higher al-mndanne and sensitivity of TRPV1 rhannp1R in reetnm (2008)
  • Author(s): 松本健次郎
  • Organizer: Digestive Disease Week and the 109th Annual Meeting of the American Ga
  • Place of Presentation: 米国・サンディエゴ
  • Year and Date: 2008-05-21
• [Patent(Industrial Property Rights)] (2008)
  • Inventor(s): 高山廣光、北島満里子、堀江俊治、松本健次郎
  • Industrial Property Rights Holder: 国立大学法人 千葉大学学校法人 城西大学
  • Filing Date: 2008-11-28
• [Patent(Industrial Property Rights)] オピオイド鎮痛剤 (2008)
  • Inventor(s): 高山廣光, 北島満里子, 堀江俊治, 松本健次郎
  • Industrial Property Rights Holder: 国立大学法人千葉大学学校法人城西大学
  • Filing Date: 2008-11-28