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- Todd D. Gould
- Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
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- Carlos A. Zarate
- Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA 20892
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- Scott M. Thompson
- Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
説明
<jats:p> 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, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and γ-aminobutyric acid receptor modulators. </jats:p>
収録刊行物
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- Annual Review of Pharmacology and Toxicology
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Annual Review of Pharmacology and Toxicology 59 (1), 213-236, 2019-01-06
Annual Reviews