Norketamine

Norketamine

Norketamine
Systematic (IUPAC) name
2-Amino-2-(2-chlorophenyl)cyclohexan-1-one
Identifiers
CAS Registry Number
79499-59-5 (HCl)
ATC code None
PubChem CID:
ChemSpider
Chemical data
Formula C12H14ClNO
Molecular mass 223.69866 g/mol

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, which is far less active as an NMDA receptor antagonist in comparison[2] but retains activity as a potent antagonist of the α7-nicotinic acetylcholine receptor.[8][9]

See also

References

  1. ^ 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–.  
  2. ^ a b c Donald G. Barceloux (3 February 2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. pp. 112–.  
  3. ^ Howard S. Smith (21 December 2008). Current Therapy in Pain. Elsevier Health Sciences. pp. 482–.  
  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–.  
  5. ^ Bradford P. Smith (21 April 2014). Large Animal Internal Medicine. Elsevier Health Sciences. pp. 30–.  
  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.  
  7. ^ 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.  
  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.  
  9. ^ Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445–.