The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
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DOI：
10.1016/j.pharmthera.2018.05.010
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发表时间：
2018-10
影响因子：
13.5
通讯作者：
Krystal JH
中科院分区：
文献类型：
--
作者：
Abdallah CG;Sanacora G;Duman RS;Krystal JH
氯胺酮抗抑郁作用的发现为开发一种真正新型的安全、有效和快速起效的抗抑郁药物(RAADS)打开了一个突破性的机会。此外，氯胺酮的快速和强大的生物学和行为效应提供了一个独特的机会，利用该药物作为工具，深入研究动物应激和抑郁的神经生物学，并在人类中开发敏感和可重复的生物标志物。过去二十年的氯胺酮文献极大地丰富了我们对慢性应激、抑郁和RAADS的机制的理解。然而，考虑到氯胺酮的药代动力学和体内药效学的复杂性，一些问题仍然没有得到回答，有时甚至被回答的问题仍然被认为是有争议的，或者至少没有被完全理解。目前的观点论文将总结我们对抑郁症的神经生物学的理解，以及氯胺酮和其他RAAD的作用机制。综述将集中在谷氨酸神经传递的作用上，回顾谷氨酸抑制和谷氨酸激活假说的历史，提出慢性应激病理的突触连接模型，并描述氯胺酮的作用机制。它还将总结可能的RAADS的临床疗效发现，提出相关的人类生物标记物发现，并讨论当前的挑战和未来的方向。
The discovery of the antidepressant effects of ketamine has opened a breakthrough opportunity to develop a truly novel class of safe, effective, and rapid-acting antidepressants (RAADs). In addition, the rapid and robust biological and behavioral effects of ketamine offered a unique opportunity to utilize the drug as a tool to thoroughly investigate the neurobiology of stress and depression in animals, and to develop sensitive and reproducible biomarkers in humans. The ketamine literature over the past two decades has considerably enriched our understanding of the mechanisms underlying chronic stress, depression, and RAADs. However, considering the complexity of the pharmacokinetics and in vivo pharmacodynamics of ketamine, several questions remain unanswered and, at times, even answered questions continue to be considered controversial or at least not fully understood. The current perspective paper will summarize our understanding of the neurobiology of depression, and the mechanisms of action of ketamine and other RAADs. The review will focus on the role of glutamate neurotransmission – reviewing the history of the “glutamate inhibition” and “glutamate activation” hypotheses, proposing a synaptic connectivity model of chronic stress pathology, and describing the mechanism of action of ketamine. It will also summarize the clinical efficacy findings of putative RAADs, present relevant human biomarker findings, and discuss current challenges and future directions.
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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.
影响因子：
7.6
作者：
Abdallah, Chadi G.;Averill, Lynnette A.;Murrough, James W.
通讯作者：
Murrough, James W.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
2.5
作者：
Averill LA;Purohit P;Averill CL;Boesl MA;Krystal JH;Abdallah CG
通讯作者：
Abdallah CG
DOI：
10.1016/j.euroneuro.2015.04.025
发表时间：
2015-08
期刊：
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
影响因子：
--
作者：
Abdallah CG;Jackowski A;Sato JR;Mao X;Kang G;Cheema R;Coplan JD;Mathew SJ;Shungu DC
通讯作者：
Shungu DC