Norketamine

Norketamine

Systematic (IUPAC) name
2-Amino-2-(2-chlorophenyl)cyclohexan-1-one
Identifiers
CAS Number	35211-10-0 79499-59-5 (HCl)
ATC code	None
PubChem	CID: 123767
ChemSpider	110322
ChEMBL	CHEMBL1039
Chemical data
Formula	C12H14ClNO
Molecular mass	223.69866 g/mol
SMILES C1CCC(C(=O)C1)(C2=CC=CC=C2Cl)N
InChI InChI=1S/C12H14ClNO/c13-10-6-2-1-5-9(10)12(14)8-4-3-7-11(12)15/h1-2,5-6H,3-4,7-8,14H2 Key:BEQZHFIKTBVCAU-UHFFFAOYSA-N

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 (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 α₇-nicotinic acetylcholine receptor, and produces rapid 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 in vivo as an NMDA receptor antagonist. 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 α₇-nicotinic acetylcholine receptor.

See also

• Arketamine
• Esketamine