Dehydronorketamine Explained

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,^[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 (K_i = 38.95 μM for (S)-(+)-DHNK). It can be detected 7–10 days after a modest dose of ketamine, and because of this, is useful in drug detection assays.^[8]

See also

• Arketamine
• Esketamine

Notes and References

1. Book: Booker PD, Chadderton N . Intravenous Agents . Bissonnette B . Pediatric Anesthesia. https://books.google.com/books?id=yq8tAwAAQBAJ&pg=PA366. 14 May 2014. PMPH-USA. 978-1-60795-213-8. 366–.
2. Book: Lapidus KA, Mathew SJ . Ketamine in treatment-resistant depression . Mann JJ, McGrath PJ, Roose SP . Clinical Handbook for the Management of Mood Disorders. https://books.google.com/books?id=3NPvLExs7X8C&pg=PA347. 9 May 2013. Cambridge University Press. 978-1-107-06744-8 . 10.1017/CBO9781139175869.027 . 345–357 (347) .
3. Bearn J, O'Brien M . "Addicted to Euphoria": The History, Clinical Presentation, and Management of Party Drug Misuse . International Review of Neurobiology . 120 . 205–233 (225) . 2015 . 26070759 . 10.1016/bs.irn.2015.02.005 . Elsevier Science . 978-0-12-803003-5 . Taba P, Lees A, Sikk K .
4. Moaddel R, Abdrakhmanova G, Kozak J, Jozwiak K, Toll L, Jimenez L, Rosenberg A, Tran T, Xiao Y, Zarate CA, Wainer IW . 6 . 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 . January 2013 . 23183107 . 3534778 . 10.1016/j.ejphar.2012.11.023 .
5. Book: Lester RA . Nicotinic Receptors. 11 November 2014. Springer. 978-1-4939-1167-7. 445–.
6. Paul RK, Singh NS, Khadeer M, Moaddel R, Sanghvi M, Green CE, O'Loughlin K, Torjman MC, Bernier M, Wainer IW . 6 . (R,S)-Ketamine metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine increase the mammalian target of rapamycin function . Anesthesiology . 121 . 1 . 149–159 . July 2014 . 24936922 . 4061505 . 10.1097/ALN.0000000000000285 .
7. Sałat K, Siwek A, Starowicz G, Librowski T, Nowak G, Drabik U, Gajdosz R, Popik P . 6 . Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor . Neuropharmacology . 99 . 301–307 . December 2015 . 26240948 . 10.1016/j.neuropharm.2015.07.037 . 19880543 .
8. Book: Xu QA . Ultra-High Performance Liquid Chromatography and Its Applications. 1 April 2013. John Wiley & Sons. 978-1-118-53398-7. 1–.