From Wikipedia, the free encyclopedia
Chemical compound
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
α3 β4 -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]
See also
References
^
a
b Booker PD, Chadderton N (14 May 2014).
"Intravenous Agents" . In Bissonnette B (ed.). Pediatric Anesthesia . PMPH-USA. pp. 366–.
ISBN
978-1-60795-213-8 .
^
a
b Lapidus KA, Mathew SJ (9 May 2013).
"Ketamine in treatment-resistant depression" . In Mann JJ, McGrath PJ, Roose SP (eds.). Clinical Handbook for the Management of Mood Disorders . Cambridge University Press. pp. 345–357 (347).
doi :
10.1017/CBO9781139175869.027 .
ISBN
978-1-107-06744-8 .
^ Bearn J, O'Brien M (2015). Taba P, Lees A, Sikk K (eds.).
" "Addicted to Euphoria": The History, Clinical Presentation, and Management of Party Drug Misuse" . International Review of Neurobiology . 120 . Elsevier Science: 205–233 (225).
doi :
10.1016/bs.irn.2015.02.005 .
ISBN
978-0-12-803003-5 .
PMID
26070759 .
^
a
b Moaddel R, Abdrakhmanova G, Kozak J, Jozwiak K, Toll L, Jimenez L, et al. (January 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 .
PMC
3534778 .
PMID
23183107 .
^ Lester RA (11 November 2014).
Nicotinic Receptors . Springer. pp. 445–.
ISBN
978-1-4939-1167-7 .
^ Paul RK, Singh NS, Khadeer M, Moaddel R, Sanghvi M, Green CE, et al. (July 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 .
PMC
4061505 .
PMID
24936922 .
^ Sałat K, Siwek A, Starowicz G, Librowski T, Nowak G, Drabik U, et al. (December 2015). "Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor". Neuropharmacology . 99 : 301–307.
doi :
10.1016/j.neuropharm.2015.07.037 .
PMID
26240948 .
S2CID
19880543 .
^ Xu QA (1 April 2013).
Ultra-High Performance Liquid Chromatography and Its Applications . John Wiley & Sons. pp. 1–.
ISBN
978-1-118-53398-7 .
nAChRs Tooltip Nicotinic acetylcholine receptors
Agonists (and
PAMs Tooltip positive allosteric modulators )
5-HIAA
6-Chloronicotine
A-84,543
A-366,833
A-582,941
A-867,744
ABT-202
ABT-418
ABT-560
ABT-894
Acetylcholine
Altinicline
Anabasine
Anatabine
Anatoxin-a
AR-R17779
Bephenium hydroxynaphthoate
Butinoline
Butyrylcholine
Carbachol
Choline
Cotinine
Cytisine
Decamethonium
Desformylflustrabromine
Dianicline
Dimethylphenylpiperazinium
Epibatidine
Epiboxidine
Ethanol (alcohol)
Ethoxysebacylcholine
EVP-4473
EVP-6124
Galantamine
GTS-21
Ispronicline
Ivermectin
JNJ-39393406
Levamisole
Lobeline
MEM-63,908 (RG-3487)
Morantel
Nicotine (
tobacco )
NS-1738
PHA-543,613
PHA-709,829
PNU-120,596
PNU-282,987
Pozanicline
Pyrantel
Rivanicline
RJR-2429
Sazetidine A
SB-206553
Sebacylcholine
SIB-1508Y
SIB-1553A
SSR-180,711
Suberyldicholine
Suxamethonium (succinylcholine)
Suxethonium (succinyldicholine)
TC-1698
TC-1734
TC-1827
TC-2216
TC-5214
TC-5619
TC-6683
Tebanicline
Tribendimidine
Tropisetron
UB-165
Varenicline
WAY-317,538
XY-4083
Antagonists (and
NAMs Tooltip negative allosteric modulators )
Precursors (and
prodrugs )