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

Deutschenbaur, Lorenz; Beck, Johannes; Kiyhankhadiv, Anna; Mühlhauser, Markus; Borgwardt, Stefan; Walter, Marc; Hasler, Gregor; Sollberger, Daniel; Lang, Undine E (2016). Role of calcium, glutamate and NMDA in major depression and therapeutic application. Progress in neuro-psychopharmacology & biological psychiatry, 64, pp. 325-333. Elsevier 10.1016/j.pnpbp.2015.02.015

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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 α-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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy
04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Healthcare Research

UniBE Contributor:

Hasler, Gregor

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0278-5846

Publisher:

Elsevier

Language:

English

Submitter:

Gregor Hasler

Date Deposited:

18 Jan 2016 12:04

Last Modified:

18 Jan 2016 12:04

Publisher DOI:

10.1016/j.pnpbp.2015.02.015

PubMed ID:

25747801

Uncontrolled Keywords:

NMDA; depression; calcium; ketamine; BDNF; GSK3; PI3K; mTOR

BORIS DOI:

10.7892/boris.74437

URI:

https://boris.unibe.ch/id/eprint/74437

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