Psychiatry and Clinical Neurosciences

Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

This historic review (2019) examines cellular mechanisms underlying the antidepressant effects of the R(-) and S(+) ketamine enantiomers and their norketamine and hydroxynorketamine metabolites. Although S(+) ketamine exhibits greater affinity to the NMDAR, which is believed to be the mediator of its antidepressant effect, preclinical evidence from animal models suggests that (R)-ketamine exerts greater potency and longer-lasting antidepressant effects with less detrimental side-effects. Given that the phase I clinical studies on R(-)ketamine and hydroxynorketamine are now underway, future studies will be able to perform a direct comparison of their efficacy to treat patients with depression.

Published

October 1, 2019

Journal

Psychiatry and Clinical Neurosciences

Authors

Hashimoto, K.