Norketamine

Norketamine
Clinical data
ATC code	None;
Legal status
Legal status	CA: Schedule I; UK: Class B;
Identifiers
	IUPAC name 2-Amino-2-(2-chlorophenyl)cyclohexan-1-one;
CAS Number	35211-10-0 ; 79499-59-5 (HCl);
PubChem CID	123767;
ChemSpider	110322;
UNII	XQY6JVF94X;
ChEMBL	ChEMBL1039;
CompTox Dashboard (EPA)	DTXSID40891434 ;
Chemical and physical data
Formula	C12H14ClNO
Molar mass	223.69866 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CCC(C(=O)C1)(C2=CC=CC=C2Cl)N;
	InChI 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 (K_i = 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 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, 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.
^ 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.

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[AdamsCashman2002-1] 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.

[Barceloux2012-2] 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.

[Smith2008-3] Howard S. Smith (21 December 2008). Current Therapy in Pain. Elsevier Health Sciences. pp. 482–. ISBN 1-4377-1117-0.

[StanleySchafer2012-4] 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.

[Smith2014-5] Bradford P. Smith (21 April 2014). Large Animal Internal Medicine. Elsevier Health Sciences. pp. 30–. ISBN 978-0-323-08840-4.

[PaulSingh2014-6] 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.

[pmid26240948-7] 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.

[MoaddelAbdrakhmanova2013-8] 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.

[Lester2014-9] Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445–. ISBN 978-1-4939-1167-7.

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See also

References