Norketamine, or N-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist (Ki = 1.7 µM and 13 µM for (S)-(+)-norketamine and (R)-(–)-norketamine, respectively), but is about 3–5 times less potent as an anesthetic in comparison. Also, similarly again to ketamine, norketamine binds to the μ- and κ-opioid receptors. Relative to ketamine, norketamine is much more potent as an antagonist of the α7-nicotinic acetylcholine receptor, and produces rapid antidepressant effects in animal models which have been reported to correlate with its activity at this receptor. However, norketamine is about 1/5th as potent as ketamine as an antidepressant in mice as per the forced swim test, and this seems also to be in accordance with its 3–5-fold reduced comparative potency in vivo as an NMDA receptor antagonist. Norketamine is metabolized into dehydronorketamine and hydroxynorketamine, which are far less or negligibly active as NMDA receptor antagonists in comparison but retain activity as potent antagonists of the α7-nicotinic acetylcholine receptor.
- 1 2 A. P. Adams; J. N. Cashman; R. M. Grounds (12 January 2002). Recent Advances in Anaesthesia and Intensive Care:. Cambridge University Press. pp. 42–. ISBN 978-1-84110-117-0.
- 1 2 3 Donald G. Barceloux (3 February 2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. pp. 112–. ISBN 978-1-118-10605-1.
- ↑ Howard S. Smith (21 December 2008). Current Therapy in Pain. Elsevier Health Sciences. pp. 482–. ISBN 1-4377-1117-0.
- ↑ T.H. Stanley; P.G. Schafer (6 December 2012). Pediatric and Obstetrical Anesthesia: Papers presented at the 40th Annual Postgraduate Course in Anesthesiology, February 1995. Springer Science & Business Media. pp. 372–. ISBN 978-94-011-0319-0.
- ↑ Bradford P. Smith (21 April 2014). Large Animal Internal Medicine. Elsevier Health Sciences. pp. 30–. ISBN 978-0-323-08840-4.
- ↑ Paul, Rajib K.; Singh, Nagendra S.; Khadeer, Mohammed; Moaddel, Ruin; Sanghvi, Mitesh; Green, Carol E.; O’Loughlin, Kathleen; Torjman, Marc C.; Bernier, Michel; Wainer, Irving W. (2014). "(R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function". Anesthesiology. 121 (1): 149–159. doi:10.1097/ALN.0000000000000285. ISSN 0003-3022. PMID 24936922.
- ↑ Sałat K, Siwek A, Starowicz G, Librowski T, Nowak G, Drabik U, et al. (2015). "Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor". Neuropharmacology. 99: 301–7. doi:10.1016/j.neuropharm.2015.07.037. PMID 26240948.
- ↑ Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W. (2013). "Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors". European Journal of Pharmacology. 698 (1-3): 228–234. doi:10.1016/j.ejphar.2012.11.023. ISSN 0014-2999.
- ↑ Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445–. ISBN 978-1-4939-1167-7.