Raffa R B, Pergolizzi J V, Taylor R
University of Arizona College of Pharmacy, Tucson, AZ, USA.
Temple University School of Pharmacy, Philadelphia, PA, USA.
J Clin Pharm Ther. 2018 Apr;43(2):308-311. doi: 10.1111/jcpt.12656. Epub 2017 Nov 26.
An effective rapid-onset treatment for major depressive disorder could save lives. Extensive preclinical and clinical data demonstrate such an action of ketamine. However, the presumptive mechanism of action, inhibition of NMDA (N-methyl-D-aspartate) receptors, has recently been challenged. Elucidation of the mechanism is important clinically for drug discovery and for understanding the (patho)physiology of depression.
The best-known pharmacologic property of ketamine is non-competitive inhibition of the NMDA subtype of glutamate receptor. Although other mechanisms have been postulated, this action has been assumed the major one that accounts for ketamine's antidepressant effect. However, a ketamine metabolite and a different mechanism have now been claimed to be necessary and sufficient for the effect.
A metabolite has been proposed to be responsible for the antidepressant action of ketamine, via activation of non-NMDA receptors. It will be important to determine which of the competing views is correct.
一种有效的快速起效的重度抑郁症治疗方法可以挽救生命。大量临床前和临床数据证明了氯胺酮有这样的作用。然而，其假定的作用机制，即抑制N-甲基-D-天冬氨酸（NMDA）受体，最近受到了挑战。阐明该机制在临床上对于药物研发以及理解抑郁症的（病理）生理学都很重要。
氯胺酮最广为人知的药理特性是对谷氨酸受体NMDA亚型的非竞争性抑制。尽管有人提出了其他机制，但一直认为这一作用是氯胺酮抗抑郁作用的主要机制。然而，现在有人声称一种氯胺酮代谢物和一种不同的机制对于该作用是必要且充分的。
有人提出一种代谢物通过激活非NMDA受体而负责氯胺酮的抗抑郁作用。确定哪种相互竞争的观点正确将很重要。
