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Ketamine for the Treatment of Depression and Other Anxiety-Related Disorders

Inventors: Panos Zanos, Ruin Moaddel, Patrick J. Morris, Irving W. Wainer, Craig J. Thomas, Carlos A. Zarate, Jr., & Todd D. Gould
Ref. No.: E-092-2011, E-116-2016 and E-036-2016

Abstract: In a new finding that could improve the treatment of depression and other related disorders, NIH researchers and their collaborators found that the metabolism of ketamine is critical to its antidepressant effects and that the (2R,6R)-2-amino-2-(2-chlorophenyl)-6- hydroxycyclohexanone ((2R,6R)-hydroxynorketamine (HNK)) metabolite reversed depression-like behaviors in mice without triggering anesthetic, dissociative or addictive side effects associated with ketamine.

Specifically, the researchers found that the metabolite does not inhibit the non-competitive glutamatergic N-methyl-D-aspartate (NMDA) receptor and that it exerts rapid actions that activate the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Results indicate that a non-NMDA receptor dependent mechanism underlying ketamine’s antidepressant properties, which involve bioactivity of a specific metabolite (2R, 6R-HNK), could be exploited for drug development. This ketamine metabolite and associated methods of treatment are available for collaboration and licensing.


NMDAR inhibition-independent antidepressant actions of ketamine metabolites. • Nature • May 4, 2016 • NCATS Chemical Genomics Center


Last updated: 11-10-2016
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