Hydroxynorketamine Blocks N-Methyl-d-Aspartate Receptor Currents by Binding to Closed Receptors.

ABSTRACT: Ketamine, a dissociative anesthetic, is experiencing a clinical resurgence as a fast-acting antidepressant. In the central nervous system, ketamine acts primarily by blocking NMDA receptor currents. Although it is generally safe in a clinical setting, it can be addictive, and several of its derivatives are being investigated as preferable alternatives. 2R,6R-Hydroxynorketamine (HNK), a ketamine metabolite, reproduces some of the therapeutic effects of ketamine and appears to lack abuse liability. Here, we report a systematic investigation of the effects of HNK on macroscopic responses elicited from recombinant NMDA receptors expressed in human embryonic kidney 293 cells. We found that, like ketamine, HNK reduced NMDA receptor currents in a dose-, pH-, and voltage-dependent ma

SUBMITTER: Abbott JA 

PROVIDER: S-EPMC7406986 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature