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Systematic (IUPAC) name
Clinical data
AHFS/ Consumer Drug Information
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CAS number 33643-46-8 N
ATC code N01AX14
PubChem CID 182137
DrugBank DB01221
ChemSpider 158414 N
Chemical data
Formula C13H16ClNO 
Mol. mass 237.725 g/mol
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Main article: Ketamine

Esketamine (also (S)-ketamine or S(+)-ketamine) (brand: Ketanest S) is a general anaesthetic and a dissociative. It is the S(+) enantiomer of the drug ketamine, a general anaesthetic. Esketamine is primarily an NMDA receptor antagonist. As of July 2013, it is being tested in US FDA clinical trials as an antidepressant.


Esketamine is approximately twice as potent as racemic ketamine.[1] Esketamine is eliminated from the human body more quickly than R(-)-ketamine or racemic ketamine, although R(-)-ketamine slows its elimination.[2]

A number of studies have suggested that esketamine has a more medically useful pharmacological action than R(-)-ketamine or racemic ketamine. Esketamine inhibits dopamine transporters eight times more than R(-)-ketamine.[3] This increases dopamine activity in the brain. At doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients.[4][5] Patients also generally recover mental function more quickly after being treated with pure esketamine, which may be a result of the fact that it is cleared from their system more quickly.[1][6]

Esketamine has an affinity for the PCP binding site of the NMDA receptor 3-4 times higher than that of R(-)-ketamine. Unlike R(-)-ketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while R(-)-ketamine decreases glucose metabolism in the brain. This difference may be responsible for the fact that esketamine generally has a more psychedelic or hallucinatory effect while R(-)-ketamine is reported to be more relaxing.[6] However, other studies have found no difference between the isomers in the patient's level of vigilance.[4]

Potential use as an antidepressant[edit]

Johnson & Johnson is developing a nasal spray formulation of esketamine as a treatment for depression in patients that have been unresponsive to other antidepressants. As of July 2013, Phase 1 clinical trial of intranasal esketamine sponsored by the Johnson & Johnson subsidiary Janssen Pharmaceutica is underway with 58 participants in Belgium.[7] AstraZeneca (AZN) is studying lanicemine, and Naurex Inc. and Cerecor Inc. are also in the process of developing new antidepressant drugs that act similarly to ketamine.[7]

Although most studies suggest that esketamine is preferable for medical uses, a 2013 study found that the antidepressant effect of R(-)-ketamine lasted longer than those of S(+)-ketamine in mice.[8]

See also[edit]


  1. ^ a b Himmelseher, S.; Pfenninger, E. (2008). "Die klinische Anwendung von S-(+)-Ketamin - eine Standortbestimmung". AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie 33 (12): 764–770. doi:10.1055/s-2007-994851. PMID 9893910.  edit
  2. ^ Ihmsen, H.; Geisslinger, G.; Schüttler, J. (2001). "Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine". Clinical pharmacology and therapeutics 70 (5): 431–438. doi:10.1067/mcp.2001.119722. PMID 11719729.  edit
  3. ^ Nishimura, M.; Sato, K. (1999). "Ketamine stereoselectively inhibits rat dopamine transporter". Neuroscience letters 274 (2): 131–134. doi:10.1016/S0304-3940(99)00688-6. PMID 10553955.  edit
  4. ^ a b Doenicke, A.; Kugler, J.; Mayer, M.; Angster, R.; Hoffmann, P. (1992). "Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings". Der Anaesthesist 41 (10): 610–618. PMID 1443509.  edit
  5. ^ Pfenninger, E.; Baier, C.; Claus, S.; Hege, G. (1994). "Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses". Der Anaesthesist. 43 Suppl 2: S68–S75. PMID 7840417.  edit
  6. ^ a b Vollenweider, F. X.; Leenders, K. L.; Oye, I.; Hell, D.; Angst, J. (1997). "Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)". European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 7 (1): 25–38. doi:10.1016/S0924-977X(96)00042-9. PMID 9088882.  edit
  7. ^ a b "From Party Drug To Antidepressant: Johnson & Johnson Vs. Rivals". Seeking Alpha. July 10, 2013. 
  8. ^ Zhang, J. C.; Li, S. X.; Hashimoto, K. (2014). "R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine". Pharmacology Biochemistry and Behavior 116: 137–141. doi:10.1016/j.pbb.2013.11.033. PMID 24316345.  edit