NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Nature April 24, 2016 P. Zanos, R. Moaddel, Patrick J. Morris et al. 1,602 citations
A metabolite of ketamine, (2R,6R)-hydroxynorketamine (HNK), produces rapid and sustained antidepressant-like effects in mice without the side effects associated with ketamine itself. These effects do not rely on blocking NMDA receptors but instead involve early and ongoing activation of AMPA receptors. This finding points to a new mechanism for developing faster-acting antidepressants with fewer unwanted effects.