Cited by 133Treatment of Major DepressionElectroconvulsive Therapy StudiesNeuroscience and Neuropharmacology Research

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Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

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Lener, Marc S., Kadriu, Bashkim, Zarate, Carlos A.·2017·Drugs

DOI 10.1007/s40265-017-0702-8PMC PMC5342919

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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.

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Authors: Lener, M. S., Kadriu, B., & Zarate, C. A.
Affiliations: National Institutes of Health (US)
Corresponding author: Lener, Marc S.
ORCID: Kadriu, Bashkim
Zarate, Carlos A.
Venue: Drugs
Publisher: Springer Science and Business Media LLC
Published: 2017-02-14
Volume: 77
Issue: 4
Pages: 381-401
ISSN: 0012-6667 (ISSN-L)
1179-1950
DOI: 10.1007/s40265-017-0702-8
PMC: PMC5342919
OpenAlex: W2588408561
Cited by: 131
References: 131
Citations by year: 2026: 2 · 2025: 10 · 2024: 11 · 2023: 16 · 2022: 18 · 2021: 17 · 2020: 19 · 2019: 14 · 2018: 15 · 2017: 9
FWCI: 2.01
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Drugs (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
Funders: National Institute of Mental Health (ZIA-MH002857-10)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: ketamine, depression, major depressive disorder, bipolar depression, antidepressant repurposing, subanesthetic ketamine, D-cycloserine, riluzole, CP-101,606, dextromethorphan, nitrous oxide, esketamine, glutamatergic signaling
MeSH terms: Depression, Humans, Ketamine, Excitatory Amino Acid Agents

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Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

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