title: Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression.
abstract: Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review highlights the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine, riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide, GLYX-13, and esketamine.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10/CRC, Room 7-5545, Bethesda, MD, USA. marc.lener@nih.gov.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Lener
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10/CRC, Room 7-5545, Bethesda, MD, USA.
authors.forename: Bashkim
authors.initials: B
authors.lastname: Kadriu
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10/CRC, Room 7-5545, Bethesda, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D003863:Depression / Q000188:drug therapy*; D018683:Excitatory Amino Acid Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018683:Excitatory Amino Acid Agents; D007649:Ketamine