(R)‐Ketamine exerts antidepressant actions partly via conversion to (2R,6R)‐hydroxynorketamine, while causing adverse effects at sub‐anaesthetic doses
British Journal of Pharmacology2019Vol. 176(14), pp. 2573–2592
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Panos Zanos, Jaclyn N. Highland, Xin Liu, Timothy A. Troppoli, Polymnia Georgiou, Jacqueline Lovett, Patrick J. Morris, Brent W. Stewart, Craig J. Thomas, Scott M. Thompson, Ruin Moaddel, Todd D. Gould
Abstract
Metabolism of (R)-ketamine to (2R,6R)-HNK increases the potency of (R)-ketamine to exert antidepressant-relevant actions in mice. Adverse effects of (R)-ketamine require higher doses than those necessary for antidepressant-sensitive behavioural changes in mice. However, our data revealing that (R)-ketamine's adverse effects are elicited at sub-anaesthetic doses indicate a potential risk for sensory dissociation and abuse liability.
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