Maj Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Trace Elements Neurobiology , Krakow , Poland.
Expert Rev Neurother. 2019 Nov;19(11):1055-1067. doi: 10.1080/14737175.2019.1643237. Epub 2019 Jul 22.
: Current antidepressant therapies exhibit low therapeutic efficiency and delayed onset of antidepressant action. Thus, the search for better acting agents is a continuous process. One of the primary targets for the development of new antidepressant drugs is the glutamate N-methyl-D-aspartate (NMDA) receptor. : The present review aims to summarize and provide an update on published preclinical data evaluating the antidepressant efficacy of various NMDA antagonists and their mechanisms of action. The review also provides an update on the clinical efficacy of ketamine and esketamine as well as other NMDA receptor antagonists based on published results from clinical studies. : The recent approval of esketamine by the FDA for the treatment of major depressive disorder (MDD) culminates the almost 30 years of research focused on the NMDA receptor as a target for the development of antidepressants. This action gives hope to patients who do not respond to currently available pharmacotherapy. While knowledge of the mechanism of action of ketamine/esketamine will pave the way for the creation of a new class of antidepressants, recent results have shown that several issues regarding the use of these compounds or other NMDA receptor antagonists must be clarified.
目前的抗抑郁治疗方法显示出疗效低和抗抑郁作用起效慢的特点。因此，寻找更好作用的药物是一个持续的过程。开发新型抗抑郁药物的主要靶点之一是谷氨酸 N-甲基-D-天冬氨酸（NMDA）受体。
本综述旨在总结和提供已发表的评价各种 NMDA 拮抗剂的抗抑郁疗效及其作用机制的临床前数据。该综述还根据临床研究的结果，提供了氯胺酮和艾司氯胺酮以及其他 NMDA 受体拮抗剂的临床疗效的最新信息。
美国食品和药物管理局（FDA）最近批准艾司氯胺酮用于治疗重度抑郁症（MDD），这标志着近 30 年来专注于 NMDA 受体作为开发抗抑郁药靶点的研究达到了高潮。这一举措给那些对现有药物治疗没有反应的患者带来了希望。虽然对氯胺酮/艾司氯胺酮作用机制的了解将为创造一类新的抗抑郁药铺平道路，但最近的结果表明，必须澄清使用这些化合物或其他 NMDA 受体拮抗剂的几个问题。
