Role of calcium, glutamate and NMDA in major depression and therapeutic application.
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.
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Lorenz
L
Deutschenbaur
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Johannes
J
Beck
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Anna
A
Kiyhankhadiv
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Markus
M
Mühlhauser
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Stefan
S
Borgwardt
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Marc
M
Walter
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Gregor
G
Hasler
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland.
Daniel
D
Sollberger
Department of Psychiatry and Psychotherapy (UPK), University Hospital of Basel, Basel, Switzerland. Electronic address: undine.lang@upkbs.ch.
Undine E
UE
Lang
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D016202:N-Methylaspartate / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002118:Calcium
BDNF; GSK3; NMDA; PI3K; calcium; depression; ketamine; mTOR