ABSTRACT
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants since this drug causes rapid-onset and sustained antidepressant effects in treatment resistant patients with depression. There are unanswered questions about how ketamine induces its rapid and sustained antidepressant actions. This key article suggests that (2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine, shows antidepressant effects in rodent models of depression, indicating that the metabolism of (R)-ketamine to (2R,6R)-HNK is pivotal in its antidepressant action. Here these findings are put into context and their significance is discussed.
Declaration of interest
K. Hashimoto is an inventor on a filed patent application on ‘The use of R-ketamine in the treatment of psychiatric diseases’ by Chiba University and has received research support from Dainippon Sumitomo, Mochida, Otsuka, and Taisho. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.