Role of calcium, glutamate and NMDA in major depression and therapeutic application

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• 作者：Lorenz Deutschenbaur¹ ; Johannes Beck¹ ; Anna Kiyhankhadiv ; Markus Mü ; hlhauser ; Stefan Borgwardt ; Marc Walter ; Gregor Hasler ; Daniel Sollberger¹ ; Undine E. Lang ; ¹ ; ^{undine.lang@upkbs.ch" class="auth_mail" title="E-mail the corresponding author}
• 关键词：N-methyl-D-aspartate ; (NMDA) ; gamma-aminobutyric acid ; (GABA) ; brain-derived neurotrophic factor ; (BDNF) ; excitatory amino acid transporters ; (EAAT) ; long-term potentiation ; (LTP) ; calmodulin-dependent protein kinase II ; (CaMKII) ; glycogen synthase kinase ; (GSK3) ; phosphoinositol-dependent kinase 3 ; (PI3K) ; NMDA receptor subtype 2B ; (NR2B)
• 刊名：Progress in Neuropsychopharmacology & Biological Psychiatry
• 出版年：2016
• 出版时间：4 January 2016
• 年：2016
• 卷：64
• 期：Complete
• 页码：325-333
• 全文大小：706 K

文摘

Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-d-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, d-cycloserine, d-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression.