title: NMDA receptor antagonists for depression: Critical considerations.
abstract: BACKGROUND
  Research studies suggest that glutamate dysfunction, in particular N-methyl-D-aspartate receptors (NMDARs) abnormalities, may be involved in the pathophysiology of major neuropsychiatric conditions. Increased glutamatergic excitotoxic activity may be found in some brain circuits of patients with major depression. According to several published reports, NMDAR antagonists may exert antidepressant activity, but the molecular changes associated with abnormal glutamatergic neurotransmission remain unclear.
  
  
  METHODS
  We have critically reviewed the current literature in order to investigate the role of NMDAR antagonists in major depression.
  
  
  RESULTS
  NMDAR antagonists, such as ketamine, may be considered novel and promising pharmacological options for the rapid treatment of treatment-resistant depression patients. This is in contrast to the delayed action of the currently available antidepressant medications. Studies suggest that glutamatergic receptor modulation may enhance neuroplasticity mechanisms and neurogenesis together with the release of some neurotransmitters. Unfortunately, the use of ketamine is currently limited by some transient adverse events, including dissociative symptoms.
  
  
  CONCLUSIONS
  Targeting NMDARs using antagonists represents an important alternative antidepressant option in major depression. However, NMDAR antagonists may exert different actions based on the differential brain location of NMDAR.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy . E-MAIL: gianluca.serafini@unige.it.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Serafini
authors.forename: Xenia
authors.initials: X
authors.lastname: Gonda
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rihmer
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pompili
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.forename: Henry A
authors.initials: HA
authors.lastname: Nasrallah
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004213:Dissociative Disorders / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate