Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants.
Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants.
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DOI：
10.1146/annurev-pharmtox-010617-052811
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发表时间：
2019-01-06
影响因子：
12.5
通讯作者：
Thompson SM
中科院分区：
文献类型：
--
作者：
Gould TD;Zarate CA Jr;Thompson SM
几十年来，抑郁症的症状主要是通过直接针对单胺类大脑系统的药物来治疗的，这种药物通常需要几周时间才能产生可测量的效果，需要几个月的时间才能缓解症状。低剂量的亚麻醉剂量的(R，S)-氯胺酮(氯胺酮)可导致核心抑郁症状的快速改善，包括情绪、快感缺失和自杀念头，这些症状在单次给药后几个小时内发生，症状通常持续一周。氯胺酮这些作用的发现使人们对未来如何更有效地治疗抑郁症产生了新的概念。在这篇综述中，我们讨论了与氯胺酮和其他快速起作用的抗抑郁药物有关的临床数据，以及关于它们作用机制的药理学知识的现状。此外，我们还讨论了这类药物参与的神经生物学回路，以及可能成为下一代药物靶点的药物，例如羟基去甲氯胺酮；代谢性谷氨酸受体2/3拮抗剂；以及N-甲基-D-天冬氨酸、α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸和γ-氨基丁酸受体调节剂。
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.
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影响因子：
13.5
作者：
Abdallah CG;Sanacora G;Duman RS;Krystal JH
通讯作者：
Krystal JH
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr
影响因子：
4.8
作者：
Carreno, Flavia R.;Collins, Gregory T.;Lodge, Daniel J.
通讯作者：
Lodge, Daniel J.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH