Investigation of development of new treatment for refractory depression by modification of glutamate neuropterans mission

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390280
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nishikawa Toru 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00198441)
• Co-Investigator(Renkei-kenkyūsha): KURUMAJI Akeo 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00251504) ; YANAMOTO Naoki 東京医科歯科大学, 医学部附属病院, 講師 (70312296) ; JITOKU Daisuke 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10613854) ; UEZATO Akihito 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90547449) ; Takeuchi Takashi 東京医科歯科大学, 医学部附属病院, 講師 (70345289) ; KYONO Hoshu 東京医科歯科大学, 医学部附属病院, 助教 (70615658)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: グルタミン酸伝達 / NMDA受容体 / D-セリン / 難治性抑うつ状態 / NMDA受容体グリシン調節部位 / 内側前頭葉皮質 / キラルアミノ酸分析 / In vivo ダイアリシス

Outline of Final Research Achievements

On the basis of NMDA receptor blocking action of ketamine that has been reported to show fast-ameliorating effects on refractory depression, the molecular and cellular mechanisms underlying signaling of a NMDA receptor co-agonist, D-serine, have been investigated to obtain a clue for a novel antidepressant. It is indicated that D-serine synthesizing enzyme, serine racemase, Dsm-1 protein which modifies the tissue and extracellular contents of D-serine and zinc ion may modify the extracellular concentrations of D-serine and/or glutamate that acts on the NMDA receptor. Therefore, the three or related molecules could be candidate targets for development of a novel antidepressant that possesses an inhibitory influence on the NMDA receptor. An open-labeled clinical trial of ifenprodil, a NMDA receptor subunit antagonist (GRIN2B), has been initiated.

Free Research Field

精神医学、分子神経生物学、神経精神薬理學