TABLE 1

CNS concentrations of (2R,6R)-HNK relevant to antidepressant actions

Species	Experimental Details	Concentration
After ketamine dosing
Humans	Estimated peak unbound brain concentration after a typical antidepressant treatment (0.5 mg/kg, i.v., over 40 min)	≤37.8 ± 14.3 nM^a^,^b^,^c
Mice	Peak total (bound and unbound) brain concentrations after a dose (10 mg/kg, i.p.) frequently reported to induce relevant behavioral actions	1.54–2.46 µmol/kg^b^,^d^,^e
After (2R,6R)-HNK dosing
Mice	Peak total concentrations after a dose (10 mg/kg, i.p.) frequently reported to induce relevant behavioral actions measured in:
	a) Whole brain	10.66–17.80 µmol/kg^d^,^f^,^g^,^h
	b) CSF	18.40 µM^g
	c) Extracellular hippocampal space	7.57 ± 2.13 µMh

↵^a Peak unbound brain concentrations were estimated based upon peak plasma levels 157 ± 59.2 nM.
↵^b Concentrations correspond to racemic mixture of (2R,6R;2S,6S)-HNK.
↵^c Shaffer et al. (2019).
↵^d Zanos et al. (2016).
↵^e Zanos et al. (2019a).
↵^f Pham et al. (2018).
↵^g Yamaguchi et al. (2018).
↵^h Lumsden et al. (2019).