Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of
ketamine
Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...
which is formed by
dehydrogenation
In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...
of its metabolite
norketamine
Norketamine, or ''N''-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist, but is about 3–5 times less potent as ...
.
Though originally considered to be inactive,
DHNK has been found to act as a potent and selective
negative allosteric modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that a ...
of the
α7-nicotinic acetylcholine receptor (
IC50 = 55 nM).
For this reason, similarly to
hydroxynorketamine
Hydroxynorketamine (HNK), or 6-hydroxynorketamine, is a minor metabolite of the anesthetic, dissociative, and antidepressant drug ketamine. It is formed by hydroxylation of the intermediate norketamine, another metabolite of ketamine. As of lat ...
(HNK), it has been hypothesized that DHNK may have the capacity to produce rapid
antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
effects.
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.
DHNK is inactive at the
α3β4-nicotinic acetylcholine receptor (IC
50 > 100 μM) and is only very weakly active at the
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...
(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.
See also
*
Arketamine
Arketamine (developmental code names PCN-101, HR-071603), also known as (''R'')-ketamine or (''R'')-(−)-ketamine, is the (''R'')-(−) enantiomer of ketamine. Similarly to racemic ketamine and esketamine, the ''S''(+) enantiomer of ke ...
*
Esketamine
Esketamine, sold under the brand names Spravato (for depression (mood), depression) and Ketanest (for anesthesia) among others, is the ''S''(+) enantiomer of ketamine. It is a dissociative hallucinogen drug used as a general anesthetic and as ...
References
Amines
2-Chlorophenyl compounds
Enones
Nicotinic antagonists
Human drug metabolites
Cyclohexenes
Negative allosteric modulators
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