“…A number of HNK metabolites have been described, including the (2,4)-, (2,5)-, and Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine (2,6)-HNKs, (Desta et al, 2012;Moaddel et al, 2010;Woolf and Adams, 1987), with (2R,6R;2S,6S)-HNK being the most prevalent in the plasma of humans (Zarate et al, 2012) and in the plasma and brain of rodents (Can et al, 2016;Moaddel et al, 2016;Zanos et al, 2016) following ketamine administration. Although early studies classified (2R,6R;2S,6S)-HNK as an inactive metabolite due to its lack of anesthetic effects (Leung and Baillie, 1986), more recent studies have established the biological activity of this metabolite (Cavalleri et al, 2018;Chou et al, 2018;Faccio et al, 2018;Ho et al, 2018;Kroin et al, 2018;Moaddel et al, 2013;Paul et al, 2014;Pham et al, 2017;Singh et al, 2016;Wray et al, 2018;Yao et al, 2017;Zanos et al, 2016). Notably, it has been demonstrated that, in mice and rats, intraperitoneal (i.p.)…”