The rapid ‐onset antidepressant effect of ketamine: More surprises?

Summary What is known and objectiveAn 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. CommentThe 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. What is new and conclusionA 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. Extensive preclinical and clinical data demonstrate a rapid antidepressant action of ketamine. The presumptive mechanism of action, inhibition of NMDA (N‐methyl‐D‐aspartate) receptors, has recently been challenged because a ketamine metabolite, and a different mechanism, have been claimed to be necessary and sufficient for the effect. Elucidation of the mechanism is important clinically, ...
Source: Journal of Clinical Pharmacy and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: COMMENTARY Source Type: research