Norketamine, or , is the major N-desmethylketamine active metabolite of ketamine, which is formed mainly by CYP3A4.  Similarly to ketamine, norketamine acts as a  noncompetitive NMDA receptor antagonist (K i = 1.7 μM and 13 μM for ( S)-(+)-norketamine and ( R)-(–)-norketamine, respectively),  but is about 3–5 times less potent as an  anesthetic in comparison.  Also, similarly again to ketamine, norketamine binds to the  μ- and κ-opioid receptors. Relative to ketamine, norketamine is much more potent as an  antagonist of the α, and produces rapid 7-nicotinic acetylcholine receptor antidepressant effects in animal models which have been reported to correlate with its activity at this receptor. However, norketamine is about 1/5th as potent as ketamine as an antidepressant in mice as per the  forced swim test, and this seems also to be in accordance with its 3–5-fold reduced comparative potency as an NMDA receptor antagonist. in vivo Norketamine is metabolized into  dehydronorketamine and hydroxynorketamine, which are far less or negligibly active as NMDA receptor antagonists in comparison, but retain activity as potent antagonists of the α  7-nicotinic acetylcholine receptor. 
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