From Wikipedia, the free encyclopedia

Jump to: navigation, search
Clinical data
Trade names Ketanest S
AHFS/ Consumer Drug Information
ATC code
CAS Number
PubChem CID
Chemical and physical data
Formula C13H16ClNO
Molar mass 237.725 g/mol
3D model (Jmol)
 NYesY (what is this?)  (verify)
Main article: Ketamine

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 N-methyl-D-aspartate (NMDA) receptor antagonist, but is also a dopamine reuptake inhibitor. As of August 18, 2016, it is in phase III clinical trials for treatment-resistant depression (TRD).[1]


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

A number of studies have suggested that esketamine has a more medically useful pharmacological action than arketamine or racemic ketamine.

However a number of studies have suggested the contrary ("R ketamine appears to be a potent and safe antidepressant relative to S ketamine[4]", "(2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine[5]", "R-ketamine as a longer-lasting antidepressant compared with rapastinel[6]" ).

Esketamine inhibits dopamine transporters eight times more than arketamine.[7] 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.[8][9] 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][10] This is however in contradiction with R-ketamine being devoid of psychotomimetic side effects.[11]

Esketamine has an affinity for the PCP binding site of the NMDA receptor 3-4 times higher than that of arketamine. Unlike arketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while arketamine 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 arketamine is reportedly more relaxing.[10] However, another study found no difference between racemic and (S)-ketamine on the patient's level of vigilance.[8] Interpretation of this finding is complicated by the fact that racemic ketamine comprises 50% (S)-ketamine.

A 2013 study in mice found that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine in mice.[12]


As of 2016 Johnson & Johnson was developing a nasal spray formulation of esketamine as a treatment for depression for people that have been unresponsive to other antidepressants and phase III clinical trials of were underway.[13][1]

See also[edit]


  1. ^ a b
  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. doi:10.1055/s-2007-994851. PMID 9893910. 
  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. doi:10.1067/mcp.2001.119722. PMID 11719729. 
  4. ^ Muller, John; Pentyala, Sahana; Dilger, James; Pentyala, Srinivas (2016-10-12). "Ketamine enantiomers in the rapid and sustained antidepressant effects". Therapeutic Advances in Psychopharmacology. 6 (3): 185–192. doi:10.1177/2045125316631267. ISSN 2045-1253. PMC 4910398Freely accessible. PMID 27354907. 
  5. ^ Hashimoto, Kenji (2016-09-28). "Ketamine's antidepressant action: beyond NMDA receptor inhibition". Expert Opinion on Therapeutic Targets. 20 (11): 1–4. doi:10.1080/14728222.2016.1238899. ISSN 1744-7631. PMID 27646666. 
  6. ^ Yang, Bangkun; Zhang, Ji-Chun; Han, Mei; Yao, Wei; Yang, Chun; Ren, Qian; Ma, Min; Chen, Qian-Xue; Hashimoto, Kenji (2016-10-01). "Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 233 (19–20): 3647–3657. doi:10.1007/s00213-016-4399-2. ISSN 1432-2072. PMC 5021744Freely accessible. PMID 27488193. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ Yang, C.; Shirayama, Y.; Zhang, J.-c; Ren, Q.; Yao, W.; Ma, M.; Dong, C.; Hashimoto, K. (2015-01-01). "R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects". Translational Psychiatry. 5 (9): e632. doi:10.1038/tp.2015.136. ISSN 2158-3188. PMID 26327690. 
  12. ^ 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. 
  13. ^ Wijesinghe, Ruki (2014). "Emerging Therapies for Treatment Resistant Depression". Mental Health Clinician. College of Psychiatric and Neurologic Pharmacists. 4 (5): 226–230. ISSN 2168-9709.