[6] However, HNK does still show biological activity, having been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor (IC50 < 1 μM).

[7][8][9] This finding has led to a call of reassessment of the understanding of the rapid antidepressant effects of ketamine and their mechanisms.

[12] Moreover, the findings would explain why other NMDA receptor antagonists such as memantine, lanicemine, and traxoprodil have thus far failed to demonstrate ketamine-like antidepressant effects in human clinical trials.

[10][12] The compound is now under active investigation by researchers at NIMH for potential clinical use, and it is hoped that use of HNK instead will mitigate the various concerns (such as abuse and dissociation) of using ketamine itself in the treatment of depression.

[16][17] These findings suggest that the antidepressant-like effects of (2R,6R)-HNK may not actually be NMDA receptor-independent and that it may act in a similar manner to ketamine.

[19] (2R,6R)-HNK is under development by the National Institute of Mental Health (NIMH) in the United States for the treatment of depression.