Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, P. O. Box 56, 00014, Helsinki, Finland.
SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Pharmacol Rep. 2021 Apr;73(2):323-345. doi: 10.1007/s43440-021-00232-4. Epub 2021 Feb 20.
Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine's effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine's complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine's rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine's action.
在过去的 50 年中，氯胺酮在人类和兽医医学中都确立了其作为一种具有多种用途的重要麻醉剂的地位。最近，氯胺酮已被研究并用于多种新的适应症，从慢性疼痛到药物成瘾和创伤后应激障碍。氯胺酮具有快速抗抑郁作用的发现导致人们对理解其作用的确切机制产生了浓厚的兴趣。事实上，在过去几十年中，氯胺酮可能对精神疾病的研究和治疗进展产生了最大的影响。尽管人们一直在努力研究揭示氯胺酮治疗抑郁症作用的分子靶点，但潜在的神经生物学机制仍然难以捉摸。氯胺酮对分子机制、多种具有药理活性的代谢物以及与促进突触可塑性相关的作用机制的复杂剂量依赖性影响，使这些努力变得更加困难。本综述旨在简要概述氯胺酮的不同用途，并重点研究氯胺酮在分子、细胞和网络水平上的快速抗抑郁作用。本综述的另一个重点是提供有关抗抑郁研究中使用的不同剂量的氯胺酮的相关研究的观点。最后，该综述讨论了一些关于氯胺酮作用的最新假设。
