Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor
metabolite of
ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...
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 (Ki = 1.7 μM and 13 μM for (''S'')-(+ ...
.
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 stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds t ...
of the
α7-nicotinic acetylcholine receptor (
IC50 = 55 nM).
For this reason, similarly to
hydroxynorketamine (HNK), it has been hypothesized that DHNK may have the capacity to produce rapid
antidepressant effects.
However, unlike ketamine, norketamine, and HNK, DHNK has been found to be inactive in the
forced swim test
The behavioural despair test (or Porsolt forced swimming test) is a test, centered on a rodent's response to the threat of drowning, whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the ...
(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 (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 k ...
*
Esketamine
Esketamine, also known as (S)-ketamine or S(+)-ketamine, is the ''S''(+) enantiomer of ketamine, is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. It is sold under the brand n ...
References
Amines
Chloroarenes
Enones
Nicotinic antagonists
Human drug metabolites
Cyclohexenes
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