Esketamine

Esketamine
Clinical data
Trade namesSpravato, Ketanest, Spravado, others
Other names(S)-Ketamine; S(+)-Ketamine; JNJ-54135419
AHFS/Drugs.comMonograph
MedlinePlusa619017
License data
Pregnancy
category
Addiction
liability		Moderate[4]
Routes of
administration		Intranasal, intravenous[5]
Drug classNMDA receptor antagonist; Antidepressant; General anesthetic; Dissociative hallucinogen; Analgesic
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityIntranasal: 30–50%
Elimination half-life5 hours
Identifiers
  • (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.242.065 Edit this at Wikidata
Chemical and physical data
FormulaC13H16ClNO
Molar mass237.73 g·mol−1
3D model (JSmol)
  • CN[C@]1(c2ccccc2Cl)CCCCC1=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
  • Key:YQEZLKZALYSWHR-ZDUSSCGKSA-N ☒N
  (verify)

Esketamine, sold under the brand names Spravato (for depression) and Ketanest (for anesthesia) among others,[10][12] is the S(+) enantiomer of ketamine.[5][13] It is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine.[14]

It is specifically used as a therapy for treatment-resistant depression (TRD) and for major depressive disorder (MDD) with co-occurring suicidal ideation or behavior.[10][15] Its efficacy for depression is modest and similar to that of other antidepressants.[16][10] Esketamine is not used by infusion into a vein for depression as it is only FDA-approved in the form of a nasal spray under direct medical supervision for this indication (the parent compound ketamine is most often administered intravenously).[10][5]

Adverse effects of esketamine include dissociation, dizziness, sedation, nausea, vomiting, vertigo, numbness, anxiety, lethargy, increased blood pressure, and feelings of drunkenness.[10] Less often, esketamine can cause bladder problems.[10][17] Esketamine acts primarily as a NMDA receptor antagonist, but also has other actions.[5][13]

In the form of racemic ketamine, esketamine was first synthesized in 1962 and introduced for medical use as an anesthetic in 1970.[18] Enantiopure esketamine was introduced for medical use as an anesthetic in 1997 and as an antidepressant in 2019.[5][10][19] It is used as an anesthetic in the European Union and as an antidepressant in the United States and Canada.[19][20][21] Due to misuse liability as a dissociative hallucinogen, esketamine is a controlled substance.[18][10]

  1. ^ a b "Spravato". Therapeutic Goods Administration (TGA). 17 March 2021. Archived from the original on 9 September 2021. Retrieved 8 September 2021.
  2. ^ a b "AusPAR: Esketamine hydrochloride". Therapeutic Goods Administration (TGA). 24 May 2021. Archived from the original on 9 September 2021. Retrieved 8 September 2021.
  3. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  4. ^ Orsolini L, Salvi V, Volpe U (June 2022). "Craving and addictive potential of esketamine as side effects?". Expert Opinion on Drug Safety. 21 (6): 803–812. doi:10.1080/14740338.2022.2071422. PMID 35509224.
  5. ^ a b c d e Himmelseher S, Pfenninger E (December 1998). "[The clinical use of S-(+)-ketamine--a determination of its place]". Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie (in German). 33 (12): 764–70. doi:10.1055/s-2007-994851. PMID 9893910. S2CID 259981872.
  6. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  7. ^ "Regulatory Decision Summary - Spravato -". Health Canada. 23 October 2014. Archived from the original on 6 June 2022. Retrieved 5 June 2022.
  8. ^ "Spravato 28 mg nasal spray, solution - Summary of Product Characteristics (SmPC)". (emc). Archived from the original on 28 August 2021. Retrieved 24 November 2020.
  9. ^ "Vesierra 25 mg/ml solution for injection/infusion - Summary of Product Characteristics (SmPC)". (emc). 21 February 2020. Archived from the original on 21 April 2021. Retrieved 24 November 2020.
  10. ^ a b c d e f g h i "Spravato- esketamine hydrochloride solution". DailyMed. 6 August 2020. Archived from the original on 18 March 2021. Retrieved 26 September 2020.
  11. ^ "Spravato EPAR". European Medicines Agency (EMA). 16 October 2019. Archived from the original on 23 November 2020. Retrieved 24 November 2020.
  12. ^ "Esketamin - Anwendung, Wirkung, Nebenwirkungen | Gelbe Liste". Gelbe Liste Online (in German). Archived from the original on 24 July 2023. Retrieved 19 March 2024.
  13. ^ a b Jelen LA, Young AH, Stone JM (February 2021). "Ketamine: A tale of two enantiomers". J Psychopharmacol. 35 (2): 109–123. doi:10.1177/0269881120959644. PMC 7859674. PMID 33155503.
  14. ^ Kohrs R, Durieux ME (November 1998). "Ketamine: teaching an old drug new tricks". Anesthesia and Analgesia. 87 (5): 1186–1193. doi:10.1213/00000539-199811000-00039. PMID 9806706.
  15. ^ Cite error: The named reference pmid33726522 was invoked but never defined (see the help page).
  16. ^ Cite error: The named reference pmid34421147 was invoked but never defined (see the help page).
  17. ^ Ng J, Lui LM, Rosenblat JD, Teopiz KM, Lipsitz O, Cha DS, et al. (April 2021). "Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment". Psychopharmacology (Berl). 238 (4): 917–926. doi:10.1007/s00213-021-05767-1. PMID 33484298. S2CID 231688343.
  18. ^ a b Tyler MW, Yourish HB, Ionescu DF, Haggarty SJ (June 2017). "Classics in Chemical Neuroscience: Ketamine". ACS Chem Neurosci. 8 (6): 1122–1134. doi:10.1021/acschemneuro.7b00074. PMID 28418641.
  19. ^ a b Cite error: The named reference FDA PR was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference Drugs.com was invoked but never defined (see the help page).
  21. ^ Swainson J, McGirr A, Blier P, Brietzke E, Richard-Devantoy S, Ravindran N, et al. (November 2020). "The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur". Can J Psychiatry. 66 (2): 113–125. doi:10.1177/0706743720970860. PMC 7918868. PMID 33174760.