Dehydronorketamine

Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor metabolite of ketamine which is formed by dehydrogenation of its metabolite norketamine.[1][2] Though originally considered to be inactive,[1][2][3] DHNK has been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor (IC50 = 55 nM).[4][5] For this reason, similarly to hydroxynorketamine (HNK), it has been hypothesized that DHNK may have the capacity to produce rapid antidepressant effects.[6] However, unlike ketamine, norketamine, and HNK, DHNK has been found to be inactive in the forced swim test (FST) in mice at doses up to 50 mg/kg.[7] DHNK is inactive at the α3β4-nicotinic acetylcholine receptor (IC50 > 100 μM) and is only very weakly active at the NMDA receptor (Ki = 38.95 μM for (S)-(+)-DHNK).[4] It can be detected 7–10 days after a modest dose of ketamine, and because of this, is useful in drug detection assays.[8]

Dehydronorketamine
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • 6-Amino-6-(2-chlorophenyl)cyclohex-2-en-1-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H12ClNO
Molar mass221.68 g·mol−1
3D model (JSmol)
SMILES
  • C1CC(C(=O)C=C1)(C2=CC=CC=C2Cl)N
InChI
  • InChI=1S/C12H12ClNO/c13-10-6-2-1-5-9(10)12(14)8-4-3-7-11(12)15/h1-3,5-7H,4,8,14H2
  • Key:BXBPJMHHWPXBJL-UHFFFAOYSA-N

See also

References
  1. Bruno Bissonnette (14 May 2014). Pediatric Anesthesia. PMPH-USA. pp. 366–. ISBN 978-1-60795-213-8.
  2. J. John Mann (9 May 2013). Clinical Handbook for the Management of Mood Disorders. Cambridge University Press. pp. 347–. ISBN 978-1-107-06744-8.
  3. The Neuropsychiatric Complications of Stimulant Abuse. Elsevier Science. 1 June 2015. pp. 225–. ISBN 978-0-12-803003-5.
  4. 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.
  5. Robin A.J. Lester (11 November 2014). Nicotinic Receptors. Springer. pp. 445–. ISBN 978-1-4939-1167-7.
  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. PMC 4061505. PMID 24936922.
  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. S2CID 19880543.
  8. Q. Alan Xu (1 April 2013). Ultra-High Performance Liquid Chromatography and Its Applications. John Wiley & Sons. pp. 1–. ISBN 978-1-118-53398-7.


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