期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 59
卷 59, 期 -, 页码 213-236出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010617-052811
关键词
depression; antidepressant; ketamine; hydroxynorketamine; glutamate; AMPA receptor; NMDA receptor
资金
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002857, ZIAMH002927] Funding Source: NIH RePORTER
- Intramural NIH HHS [ZIA MH002857-14] Funding Source: Medline
- NIMH NIH HHS [R01 MH086828, R01 MH107615] Funding Source: Medline
For decades, symptoms of depression have been treated primarily with medications that directly target the monoaminergic brain systems, which typically take weeks to exert measurable effects and months to exert remission of symptoms. Low, subanesthetic doses of (R, S)-ketamine (ketamine) result in the rapid improvement of core depressive symptoms, including mood, anhedonia, and suicidal ideation, occurring within hours following a single administration, with relief from symptoms typically lasting up to a week. The discovery of these actions of ketamine has resulted in a reconceptualization of how depression could be more effectively treated in the future. In this review, we discuss clinical data pertaining to ketamine and other rapid-acting antidepressant drugs, as well as the current state of pharmacological knowledge regarding their mechanism of action. Additionally, we discuss the neurobiological circuits that are engaged by this drug class and that may be targeted by a future generation of medications, for example, hydroxynorketamine; metabotropic glutamate receptor 2/3 antagonists; and N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and gamma-aminobutyric acid receptor modulators.
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