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 (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.

References

Amines Chloroarenes Enones Nicotinic antagonists Human drug metabolites Cyclohexenes {{nervous-system-drug-stub

See also

References