BioCentury
ARTICLE | Targets & Mechanisms

Dissociating ketamine

An NMDA receptor-independent ketamine metabolite might bypass the drug's side effects

May 26, 2016 7:00 AM UTC

For decades, researchers have struggled with the conundrum of how to exploit the antidepressant effects of ketamine without incurring its psychedelic effects. Now, a group from NIH and the University of Maryland has shown that one of the drug's metabolites - (2R,6R)-hydroxynorketamine (HNK) - is responsible for the former but not the latter, and challenged the dogma that the drug works by blocking NMDA receptors. While at least one company invested in that hypothesis is sticking with it, others are lining up to license the metabolite.

The team, led by Todd Gould, an associate professor in the departments of psychiatry and anatomy, neurobiology and pharmacology at the University of Maryland, plans to test the metabolite in the clinic within a year. ...