Systematic (IUPAC) name
Clinical data
Trade names Ketanest S
Legal status
CAS number  N
ATC code N01
ChemSpider  N
Chemical data
Formula C13H16ClNO 
Mol. mass 237.725 g/mol

Esketamine (also (S)-ketamine or S(+)-ketamine) (brand name Ketanest S) is a general anaesthetic and a dissociative. It is the S(+) enantiomer of the drug ketamine, a general anaesthetic. Esketamine acts primarily as a non-competitive NMDA receptor antagonist, but is also a dopamine reuptake inhibitor. As of July 2014, it is in phase II clinical trials for treatment-resistant depression (TRD).[1]


  • Pharmacology 1
  • Potential use as an antidepressant 2
  • See also 3
  • References 4


Esketamine is approximately twice as potent as racemic ketamine.[2] It is eliminated from the human body more quickly than R(-)-ketamine or racemic ketamine, although R(-)-ketamine slows its elimination.[3]

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.[4] 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.[5][6] 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.[2][7]

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 dissociative or hallucinogenic effect while R(-)-ketamine is reportedly more relaxing.[7] However, other studies have found no difference between the isomers in the patient's level of vigilance.[5]

Potential use as an antidepressant

Johnson & Johnson is developing a nasal spray formulation of esketamine as a treatment for depression in patients that have been unresponsive to other antidepressants in the United States.[1] As of July 2014, phase II clinical trials of intranasal esketamine sponsored by the Johnson & Johnson subsidiary Janssen Pharmaceutica are underway.[1][8] Other pharmaceutical companies are also developing new antidepressant drugs that act similarly to ketamine, including Naurex's GLYX-13 and NRX-1074, and Cerecor's CERC-301.[1]

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.[9]

See also


  1. ^ a b c d Wijesinghe, R (2014). "Emerging Therapies for Treatment Resistant Depression". Ment Health Clin 4 (5): 56.  
  2. ^ a b Himmelseher, S.; Pfenninger, E. (2008). "Die klinische Anwendung von S-(+)-Ketamin - eine Standortbestimmung". AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie 33 (12): 764–770.  
  3. ^ 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.  
  4. ^ Nishimura, M.; Sato, K. (1999). "Ketamine stereoselectively inhibits rat dopamine transporter". Neuroscience letters 274 (2): 131–134.  
  5. ^ 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.  
  6. ^ 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.  
  7. ^ 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.  
  8. ^
  9. ^ 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.