Major active metabolite of ketamine
Norketamine ATC code Legal status
CA : Schedule I
UK : Class B
2-Amino-2-(2-chlorophenyl)cyclohexan-1-one
CAS Number PubChem CID ChemSpider UNII ChEMBL CompTox Dashboard (EPA ) Formula C 12 H 14 Cl N O Molar mass 223.70 g·mol−1 3D model (JSmol )
C1CCC(C(=O)C1)(C2=CC=CC=C2Cl)N
InChI=1S/C12H14ClNO/c13-10-6-2-1-5-9(10)12(14)8-4-3-7-11(12)15/h1-2,5-6H,3-4,7-8,14H2
Key:BEQZHFIKTBVCAU-UHFFFAOYSA-N
Norketamine , or N -desmethylketamine , is the major active metabolite of ketamine , which is formed mainly by CYP3A4 .[1] [2] 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),[1] [3] but is about 3–5 times less potent as an anesthetic in comparison.[2] [4] Also, similarly again to ketamine, norketamine binds to the μ- and κ-opioid receptors .[5] 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.[6] 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.[7] Norketamine is metabolized into dehydronorketamine and hydroxynorketamine , which are far less or negligibly active as NMDA receptor antagonists in comparison,[2] but retain activity as potent antagonists of the α7 -nicotinic acetylcholine receptor.[8] [9]
References [ ]
^ a b 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 .
^ a b c 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 978-1-4377-1117-2 .
^ 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 . PMC 4061505 . PMID 24936922 .
^ Sałat K, Siwek A, Starowicz G, Librowski T, Nowak G, Drabik U, Gajdosz R, Popik P (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 . S2CID 19880543 .
^ 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 . PMC 3534778 . PMID 23183107 .
^ Robin A.J. Lester (11 November 2014). Nicotinic Receptors . Springer. pp. 445–. ISBN 978-1-4939-1167-7 .
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