Clinical data
Trade names Ketanest, Ketanest S
Synonyms Esketamine hydrochloride; (S)-Ketamine; S(+)-Ketamine; JNJ-54135419
AHFS/ Consumer Drug Information
Routes of
Intravenous infusion[1]
Drug class General anesthetic; Analgesic; Dissociative hallucinogen; Antidepressant
ATC code
CAS Number
PubChem CID
Chemical and physical data
Formula C13H16ClNO
Molar mass 237.725 g/mol
3D model (JSmol)

Esketamine, also known as (S)-ketamine or S(+)-ketamine and sold under the brand names Ketanest and Ketanest S among others,[2][3][4][5] is a general anesthetic and a dissociative hallucinogen.[1] It is the S(+) enantiomer of ketamine, which is an anesthetic and dissociative similarly.[1] It is given by intravenous infusion.[1]

Esketamine acts primarily as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist.[1][6] It also acts to some extent as a dopamine reuptake inhibitor but, unlike ketamine, does not interact with the sigma receptors.[1]

Esketamine was introduced for medical use in 1997.[1] In addition to its anesthetic effects, the medication shows properties of being a rapid-acting antidepressant, and is under development for use as such.[6][7] As of November 2017, it has completed phase III clinical trials for treatment-resistant depression (TRD) in the United States, with results to be announced in the second quarter of 2018.[6][7] Johnson & Johnson plans on filing a Food and Drug Administration (FDA) New Drug Application (NDA) for approval in 2018.[8] Esketamine could be approved as soon as early 2019.[9]

Medical uses

Esketamine is a general anesthetic and is used for similar indications as ketamine.[1] Such uses include induction of anesthesia in high-risk patients such as those with hemorrhagic shock, anaphylactic shock, septic shock, severe bronchospasm, severe hepatic insufficiency, cardiac tamponade, and constrictive pericarditis; anesthesia in caesarian section; use of multiple anesthetics in burns; and as a supplement to regional anesthesia with incomplete nerve blocks.[1]


Esketamine is approximately twice as potent as an anesthetic as racemic ketamine.[10] It is eliminated from the human body more quickly than arketamine (R(–)-ketamine) or racemic ketamine, although arketamine slows its elimination.[11]

A number of studies have suggested that esketamine has a more medically useful pharmacological action than arketamine or racemic ketamine. However, in mice found that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine.[12] As such, as an antidepressant, the contrary has been stated ("R ketamine appears to be a potent and safe antidepressant relative to S ketamine",[13] "(2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine",[14] "R-ketamine as a longer-lasting antidepressant compared with rapastinel").[15]

Esketamine inhibits dopamine transporters eight times more than arketamine.[16] 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.[17][18] 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.[10][19] This is however in contradiction with R-ketamine being devoid of psychotomimetic side effects.[20]

Esketamine has an affinity for the PCP binding site of the NMDA receptor 3 to 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.[19] However, another study found no difference between racemic and (S)-ketamine on the patient's level of vigilance.[17] Interpretation of this finding is complicated by the fact that racemic ketamine comprises 50% (S)-ketamine.


Esketamine was introduced for medical use in Germany in 1997, and was subsequently marketed in other countries.[1][21]

Society and culture

Generic names

Esketamine is the generic name of the drug and its INN and BAN, while esketamine hydrochloride is its BANM.[21] It is also known as S(+)-ketamine, (S)-ketamine, or (–)-ketamine, as well as by its developmental code name JNJ-54135419.[21][7]

Brand names

Esketamine is marketed under the brand names Ketanest, Ketanest S, Ketanest-S, and Keta-S (veterinary) among others.[21]


Esketamine is marketed in Europe, including in Austria, Denmark, Estonia, Finland, Germany, the Netherlands, Norway, Slovenia, Sweden, and Switzerland.[21]



Similarly to ketamine, esketamine shows a profile of being a rapid-acting antidepressant.[6][22] As such, it is currently under development by Johnson & Johnson in a nasal spray formulation under the developmental code name JNJ-54135419 for the treatment of major depressive disorder (MDD).[7][6][22] The drug is being studied specifically for use in combination with an oral antidepressant in patients with TRD who have been unresponsive to treatment.[7][6][22] As of June 2017, it is in phase III clinical trials for this indication, with six ongoing trials.[7][6][22] Esketamine has received breakthrough designation from the FDA for depression twice, specifically for TRD in November 2013 and for MDD with accompanying suicidal ideation in August 2016.[7][22] It has been said recently that esketamine seems to be the closest novel and rapid-acting antidepressant to approval for the treatment of depression.[22]

See also


  1. 1 2 3 4 5 6 7 8 9 10 Himmelseher, S.; Pfenninger, E. (2008). "[The Clinical Application of S-(+)-Ketamine]". AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie. 33 (12): 764–770. doi:10.1055/s-2007-994851. ISSN 0939-2661. PMID 9893910.
  2. "Text search results for esketamine: Martindale: The Complete Drug Reference". MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 20 August 2017.
  3. Brayfield, A, ed. (9 January 2017). "Ketamine Hydrochloride". MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 20 August 2017.
  4. Krüger, AD (1998). "[Current aspects of using ketamine in childhood]". Anaesthesiologie und Reanimation. 23 (3): 64–71. PMID 9707751.
  5. Höflich, A; Hahn, A; Küblböck, M; Kranz, GS; Vanicek, T; Ganger, S; Spies, M; Windischberger, C; Kasper, S; Winkler, D; Lanzenberger, R (April 2017). "Ketamine-dependent neuronal activation in healthy volunteers". Brain Structure & Function. 222 (3): 1533–1542. doi:10.1007/s00429-016-1291-0. PMID 27578365.
  6. 1 2 3 4 5 6 7 Rakesh G, Pae CU, Masand PS (2017). "Beyond serotonin: newer antidepressants in the future". Expert Rev Neurother. 17 (8): 1–14. doi:10.1080/14737175.2017.1341310. PMID 28598698.
  7. 1 2 3 4 5 6 7 "Esketamine - Johnson & Johnson - AdisInsight". Retrieved 7 November 2017.
  9. Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7: 659. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.
  10. 1 2 Himmelseher S, Pfenninger E (1998). "[The clinical use of S-(+)-ketamine--a determination of its place]". Anasthesiol Intensivmed Notfallmed Schmerzther (in German). 33 (12): 764–70. doi:10.1055/s-2007-994851. PMID 9893910.
  11. Ihmsen H, Geisslinger G, Schüttler J (2001). "Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine". Clin. Pharmacol. Ther. 70 (5): 431–8. doi:10.1067/mcp.2001.119722. PMID 11719729.
  12. Zhang JC, Li SX, Hashimoto K (2014). "R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine". Pharmacol. Biochem. Behav. 116: 137–41. doi:10.1016/j.pbb.2013.11.033. PMID 24316345.
  13. Muller J, Pentyala S, Dilger J, Pentyala S (2016). "Ketamine enantiomers in the rapid and sustained antidepressant effects". Ther Adv Psychopharmacol. 6 (3): 185–92. doi:10.1177/2045125316631267. PMC 4910398. PMID 27354907.
  14. Hashimoto K (2016). "Ketamine's antidepressant action: beyond NMDA receptor inhibition". Expert Opin. Ther. Targets. 20 (11): 1389–1392. doi:10.1080/14728222.2016.1238899. PMID 27646666.
  15. Yang B, Zhang JC, Han M, Yao W, Yang C, Ren Q, Ma M, Chen QX, Hashimoto K (2016). "Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 233 (19–20): 3647–57. doi:10.1007/s00213-016-4399-2. PMC 5021744. PMID 27488193.
  16. Nishimura M, Sato K (1999). "Ketamine stereoselectively inhibits rat dopamine transporter". Neurosci. Lett. 274 (2): 131–4. doi:10.1016/s0304-3940(99)00688-6. PMID 10553955.
  17. 1 2 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]". Anaesthesist (in German). 41 (10): 610–8. PMID 1443509.
  18. 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]". Anaesthesist (in German). 43 Suppl 2: S68–75. PMID 7840417.
  19. 1 2 Vollenweider FX, Leenders KL, 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)". Eur Neuropsychopharmacol. 7 (1): 25–38. doi:10.1016/s0924-977x(96)00042-9. PMID 9088882.
  20. Yang C, Shirayama Y, Zhang JC, Ren Q, Yao W, Ma M, Dong C, Hashimoto K (2015). "R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects". Transl Psychiatry. 5 (9): e632. doi:10.1038/tp.2015.136. PMC 5068814. PMID 26327690.
  21. 1 2 3 4 5
  22. 1 2 3 4 5 6 Lener MS, Kadriu B, Zarate CA (2017). "Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression" (Full text). Drugs. 77 (4): 381–401. doi:10.1007/s40265-017-0702-8. PMC 5342919. PMID 28194724.

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