Cited by 228Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchElectroconvulsive Therapy Studies

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Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism

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Aleksandrova, Lily R., Phillips, Anthony G., Wang, Yu Tian·2017·Journal of Psychiatry and Neuroscience

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Abstract

The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the molecular mechanisms mediating ketamine’s clinical efficacy as well as increased efforts to identify new targets for antidepressant action. We review the clinical utility of ketamine and recent insights into its mechanism of action as an antidepressant, including the roles of N-methyl-d-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor upregulation, activation of downstream synaptogenic signalling pathways and the production of an active ketamine metabolite, hydroxynorketamine. Emerging knowledge of the molecular mechanisms underlying both ketamine’s positive therapeutic and detrimental side effects will aid the development of a new generation of much-needed superior antidepressant agents.

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Authors: Aleksandrova, L. R., Phillips, A. G., & Wang, Y. T.
Affiliations: University of British Columbia (CA)
ORCID: Aleksandrova, Lily R.
Phillips, Anthony G.
Wang, Yu Tian
Venue: Journal of Psychiatry and Neuroscience
Publisher: Canadian Science Publishing
Published: 2017-07
Volume: 42
Issue: 4
Pages: 222-229
ISSN: 1180-4882 (ISSN-L)
1488-2434
DOI: 10.1503/jpn.160175
PMC: PMC5487269
OpenAlex: W2628731659
Cited by: 228
References: 63
Citations by year: 2026: 17 · 2025: 27 · 2024: 20 · 2023: 29 · 2022: 35 · 2021: 31 · 2020: 31 · 2019: 16 · 2018: 14 · 2017: 7
FWCI: 2.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.nrcresearchpress.com/page/about/CorporateTextAndDataMining (tdm)
Locations: Journal of Psychiatry and Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords: ketamine, antidepressant mechanism, major depressive disorder, treatment-resistant depression, NMDA receptor antagonism, AMPA receptors, hydroxynorketamine, ketamine side effects, antidepressant drug development
MeSH terms: Animals, Antidepressive Agents, Depression, Humans, Ketamine, Models, Neurological, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA

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Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism

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