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Clinical data
Trade namesSpravato, Ketanest, Vesierra, others
Other namesEsketamine hydrochloride; (S)-Ketamine; S(+)-Ketamine; JNJ-54135419
License data
Routes of
Intranasal, Intravenous infusion[3]
Drug classNMDA receptor antagonists; Antidepressants; General anesthetics; Dissociative hallucinogens; Analgesics
ATC code
Legal status
Legal status
  • (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone
CAS Number
PubChem CID
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.242.065 Edit this at Wikidata
Chemical and physical data
Molar mass237.73 g·mol−1
3D model (JSmol)
  • CN[C@](C1=C(Cl)C=CC=C1)(CCCC2)C2=O
  • InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3/t13-/m0/s1 ☒N

Esketamine, sold under the brand name Spravato[6] among others,[8][9] is a medication used as a general anesthetic and for treatment-resistant depression.[6][3] Esketamine is used as a nasal spray or by injection into a vein.[6][3]

Esketamine acts primarily as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist.[3][10] It also acts to some extent as a dopamine reuptake inhibitor but, unlike ketamine, does not interact with the sigma receptors.[3] The compound is the S(+) enantiomer of ketamine, which is an anesthetic and dissociative similarly.[3] It is unknown whether its antidepressant action is superior, inferior or equal to racemic ketamine and its opposite enantiomer, arketamine, which are both being investigated for the treatment of depression.

Esketamine was introduced for medical use in 1997.[3] In 2019, it was approved for use with other antidepressants, for the treatment of depression in adults in the United States.[11] It is basically a chiral switch of (±)-ketamine. The switch has been done for the perceived therapeutic benefits viz. Increased potency and tolerance, faster recovery.[12]

In August 2020, it was approved by the U.S. Food and Drug Administration (FDA) with the added indication for the short-term treatment of suicidal thoughts.[13]

Medical uses[edit]


Esketamine is a general anesthetic and is used for similar indications as ketamine.[3] 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.[3]


Similarly to ketamine, esketamine appears to be a rapid-acting antidepressant.[10][14] It received a breakthrough designation from the FDA for treatment-resistant depression (TRD) in 2013 and major depressive disorder (MDD) with accompanying suicidal ideation in 2016.[15][14] The medication was studied for use in combination with an antidepressant in people with TRD who had been unresponsive to treatment;[15][10][14] six phase III clinical trials for this indication were conducted in 2017.[15][10][14] It is available as a nasal spray.[15][10][14]

In February 2019, an outside panel of experts recommended that the FDA approve the nasal spray version of esketamine,[16] provided that it be given in a clinical setting, with people remaining on site for at least two hours after. The reasoning for this requirement is that trial participants temporarily experienced sedation, visual disturbances, trouble speaking, confusion, numbness, and feelings of dizziness during immediately after.[17]

In January 2020, esketamine was rejected by the National Health Service of Great Britain. NHS questioned the benefits and claimed that it was too expensive. People who have been already using the medication were allowed to complete treatment if their doctors consider this necessary.[18]

Side effects[edit]

Most common side effects when used in those with treatment resistant depression include dissociation, dizziness, nausea, sleepiness, anxiety, and increased blood pressure.[19]


Esketamine is approximately twice as potent an anesthetic as racemic ketamine.[20] It is eliminated from the human body more quickly than arketamine (R(–)-ketamine) or racemic ketamine, although arketamine slows its elimination.[21]

A number of studies have suggested that esketamine has a more medically useful pharmacological action than arketamine or racemic ketamine[citation needed] but, in mice, that the rapid antidepressant effect of arketamine was greater and lasted longer than that of esketamine.[22] The usefulness of arketamine over esketamine has been supported by other researchers.[23][24][25]

Esketamine inhibits dopamine transporters eight times more than arketamine.[26] 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.[27][28] 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.[20][29] This is however in contradiction with R-ketamine being devoid of psychotomimetic side effects.[30]

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.[29] However, another study found no difference between racemic and (S)-ketamine on the patient's level of vigilance.[27] Interpretation of this finding is complicated by the fact that racemic ketamine is 50% (S)-ketamine.[31]


Esketamine was introduced for medical use as an anesthetic in Germany in 1997, and was subsequently marketed in other countries.[3][32] In addition to its anesthetic effects, the medication showed properties of being a rapid-acting antidepressant, and was subsequently investigated for use as such.[10][15] In November 2017, it completed phase III clinical trials for treatment-resistant depression in the United States.[10][15] Johnson & Johnson filed a Food and Drug Administration (FDA) New Drug Application (NDA) for approval on 4 September 2018;[33] the application was endorsed by an FDA advisory panel on 12 February 2019, and on 5 March 2019, the FDA approved esketamine, in conjunction with an oral antidepressant, for the treatment of depression in adults.[11]

In the 1980s and '90s, closely associated ketamine was used as a club drug known as "Special K" for its trip-inducing side effects.[34][35]

Society and culture[edit]


Esketamine is the generic name of the drug and its INN and BAN, while esketamine hydrochloride is its BANM.[32] It is also known as S(+)-ketamine, (S)-ketamine, or (–)-ketamine ((-)[+] ketamine) as well as by its developmental code name JNJ-54135419.[32][15]

Esketamine is marketed under the brand name Spravato for use as an antidepressant and the brand names Ketanest, Ketanest S, Ketanest-S, Keta-S for use as an anesthetic (veterinary), among others.[32]


Esketamine is marketed as an antidepressant in the United States;[11] and as an anesthetic in the European Union.[32]

Legal status[edit]

Esketamine is a Schedule III controlled substance in the United States.[6]


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  2. ^ a b "AusPAR: Esketamine hydrochloride". Therapeutic Goods Administration (TGA). 24 May 2021. Retrieved 8 September 2021.
  3. ^ a b c d e f g h i j Himmelseher S, Pfenninger E (December 1998). "[The clinical use of S-(+)-ketamine--a determination of its place]". Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie. 33 (12): 764–70. doi:10.1055/s-2007-994851. PMID 9893910.
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  21. ^ Ihmsen H, Geisslinger G, Schüttler J (November 2001). "Stereoselective pharmacokinetics of ketamine: R(–)-ketamine inhibits the elimination of S(+)-ketamine". Clinical Pharmacology and Therapeutics. 70 (5): 431–8. doi:10.1067/mcp.2001.119722. PMID 11719729.
  22. ^ Zhang JC, Li SX, Hashimoto K (January 2014). "R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine". Pharmacology, Biochemistry, and Behavior. 116: 137–41. doi:10.1016/j.pbb.2013.11.033. PMID 24316345. S2CID 140205448.
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  35. ^ Hoffer, Lee (7 March 2019). "The FDA Approved a Ketamine-Like Nasal Spray for Hard-to-Treat Depression". Vice. Retrieved 11 February 2020.

External links[edit]