Ketamine

For the functional group referred to as ketimine, see Imine.

Ketamine
Clinical data
Trade namesKetalar, others
Other namesCI-581; CL-369; CM-52372-2[1]
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Addiction
liability		Moderate–high[3][4]
Routes of
administration		Any[5][6][7][8]
Drug classNMDA receptor antagonist; general anesthetic; dissociative hallucinogen; analgesic; antidepressant
ATC code
Legal status
Legal status
  • AU: S8 (Controlled drug)
  • BR: Class C1 (Other controlled substances)
  • CA: Schedule I
  • DE: § 48 AMG/§ 1 MPAV (Prescription only)
  • UK: Class B (Class A if prepared as an injection)
  • US: Schedule III
  • UN: Unscheduled
  • In general Rx-only
Pharmacokinetic data
Bioavailability
Protein binding23–47%[12]
MetabolismLiver, intestine (oral):
Metabolites
  • Norketamine
  • Dehydronorketamine
  • Hydroxynorketamine
Onset of action
  • Intravenous: seconds[13]
  • Intramuscular: 1–5 min[13][14]
  • Subcutaneous: 15–30 min[14]
  • Insufflation: 5–10 min[13]
  • By mouth: 15–30 min[13][14]
Elimination half-life
  • Ketamine: 2.5–3 hours[13][7]
  • Norketamine: 12 hours[14]
Duration of action
  • Intramuscular: 0.5–2 hours[14]
  • Insufflation: 45–60 min[13]
  • By mouth: 1–6+ hours[13][14]
Excretion
Identifiers
IUPAC name
  • (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.027.095
Chemical and physical data
FormulaC13H16ClNO
Molar mass237.73 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture:[13]
  • Esketamine (S(+)-isomer)
  • Arketamine (R(−)-isomer)
Melting point92[18] °C (198 °F)
SMILES
  • Clc1ccccc1C2(NC)CCCCC2=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 Y
  • Key:YQEZLKZALYSWHR-UHFFFAOYSA-N Y
  (verify)

Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management.[19][20] Ketamine exists as its two enantiomers, S- (esketamine) and R- (arketamine), and has antidepressant action likely involving additional mechanisms than NMDA antagonism.

At anesthetic doses, ketamine induces a state of dissociative anesthesia, a trance-like state providing pain relief, sedation, and amnesia.[21] Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation.[21] As an anesthetic, it is used especially in trauma, emergency, and pediatric cases. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression.

Ketamine is legally used in medicine but is also tightly controlled, as it is used as a recreational drug for its hallucinogenic and dissociative effects.[22] When used recreationally, it is found both in crystalline powder and liquid form, and is often referred to by users as "Ket", "Special K" or simply "K". The long-term effects of repeated use are largely unknown and are an area of active investigation.[23][24][25] Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes.[26] Ketamine can cause dissociation and nausea, and other adverse effects, and is contraindicated in severe heart or liver disease, and uncontrolled psychosis. Ketamine's effects are enhanced by propofol, midazolam, and naltrexone; reduced by lamotrigine, nimodipine, and clonidine; and benzodiazepines may blunt its antidepressant action.

Ketamine was first synthesized in 1962; it is derived from phencyclidine in pursuit of a safer anesthetic with fewer hallucinogenic effects.[27][28] It was approved for use in the United States in 1970.[20] It has been regularly used in veterinary medicine and was extensively used for surgical anesthesia in the Vietnam War.[29] It later gained prominence for its rapid antidepressant effects discovered in 2000, marking a major breakthrough in depression treatment. A 2023 meta-analysis concluded that racemic ketamine, especially at higher doses, is more effective and longer-lasting than esketamine in reducing depression severity. It is on the World Health Organization's List of Essential Medicines.[30] It is available as a generic medication.[31]

  1. ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 159–. ISBN 978-94-011-4439-1. Archived from the original on 11 April 2017.
  2. ^ "Ketamine (Ketalar) Use During Pregnancy". Drugs.com. 22 November 2019. Archived from the original on 26 June 2020. Retrieved 18 May 2020.
  3. ^ "Drug Scheduling". U.S. Drug Enforcement Administration. Archived from the original on 8 April 2024. Retrieved 29 December 2023. Ketamine is listed in Schedule III.
  4. ^ Huang, MC., Lin, SK. (2020). "Ketamine Abuse: Past and Present". In: Hashimoto, K., Ide, S., Ikeda, K. (eds.) Ketamine. Springer, Singapore. doi:10.1007/978-981-15-2902-3_1.
  5. ^ Bell RF, Eccleston C, Kalso EA (June 2017). "Ketamine as an adjuvant to opioids for cancer pain" (PDF). The Cochrane Database of Systematic Reviews. 6 (9): CD003351. doi:10.1002/14651858.CD003351.pub3. PMC 6481583. PMID 28657160. Archived (PDF) from the original on 12 January 2024. Retrieved 10 September 2018.{{cite journal}}: CS1 maint: article number as page number (link)
  6. ^ Moyse DW, Kaye AD, Diaz JH, Qadri MY, Lindsay D, Pyati S (March 2017). "Perioperative Ketamine Administration for Thoracotomy Pain". Pain Physician. 20 (3): 173–184. PMID 28339431.
  7. ^ a b c d e f g h Mathew SJ, Zarate Jr CA (25 November 2016). Ketamine for Treatment-Resistant Depression: The First Decade of Progress. Springer. pp. 8–10, 14–22. ISBN 978-3-319-42925-0. Archived from the original on 8 September 2017.
  8. ^ Brayfield A, ed. (9 January 2017). "Ketamine Hydrochloride: Martindale: The Complete Drug Reference". MedicinesComplete. London, UK: Pharmaceutical Press. Archived from the original on 28 August 2021. Retrieved 24 August 2017.
  9. ^ Kintz P (22 March 2014). Toxicological Aspects of Drug-Facilitated Crimes. Elsevier Science. pp. 87–. ISBN 978-0-12-416969-2. Archived from the original on 8 September 2017.
  10. ^ a b c Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, et al. (June 2013). "Ketamine: use in anesthesia". CNS Neurosci Ther. 19 (6): 381–9. doi:10.1111/cns.12072. PMC 6493613. PMID 23521979.
  11. ^ Hashimoto K (October 2019). "Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective". Psychiatry and Clinical Neurosciences. 73 (10): 613–627. doi:10.1111/pcn.12902. PMC 6851782. PMID 31215725.
  12. ^ Dayton PG, Stiller RL, Cook DR, Perel JM (1983). "The binding of ketamine to plasma proteins: emphasis on human plasma". Eur J Clin Pharmacol. 24 (6): 825–31. doi:10.1007/BF00607095. PMID 6884418. S2CID 807011.
  13. ^ a b c d e f g h Sinner B, Graf BM (2008). "Ketamine". In Schüttler J, Schwilden H (eds.). Modern Anesthetics. Handbook of Experimental Pharmacology. Vol. 182. pp. 313–33. doi:10.1007/978-3-540-74806-9_15. ISBN 978-3-540-72813-9. PMID 18175098.
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  16. ^ Hijazi Y, Boulieu R (July 2002). "Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes". Drug Metabolism and Disposition. 30 (7): 853–8. doi:10.1124/dmd.30.7.853. PMID 12065445. S2CID 15787750.
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  18. ^ Sass W, Fusari S (1977). "Ketamine". Analytical Profiles of Drug Substances. Vol. 6. Academic Press. pp. 297–322. doi:10.1016/S0099-5428(08)60347-0. ISBN 9780122608063.
  19. ^ "Ketamine". PubChem. U.S. National Library of Medicine. Retrieved 22 May 2025.
  20. ^ a b Sachdeva B, Sachdeva P, Ghosh S, Ahmad F, Sinha JK (March 2023). "Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects". Ibrain. 9 (1): 90–101. doi:10.1002/ibra.12094. ISSN 2769-2795. PMC 10528797. PMID 37786516. S2CID 257117630.
  21. ^ a b Green SM, Roback MG, Kennedy RM, Krauss B (May 2011). "Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update". Annals of Emergency Medicine. 57 (5): 449–461. doi:10.1016/j.annemergmed.2010.11.030. PMID 21256625.
  22. ^ Morgan CJ, Curran HV (January 2012). "Ketamine use: a review". Addiction. 107 (1): 27–38. doi:10.1111/j.1360-0443.2011.03576.x. PMID 21777321. S2CID 11064759.
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  26. ^ Orhurhu VJ, Vashisht R, Claus LE, Cohen SP (April 2022). "Ketamine toxicity". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31082131. Archived from the original on 16 May 2022. Retrieved 18 August 2022.
  27. ^ Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI (September 2016). "Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy". Clinical Pharmacokinetics. 55 (9): 1059–77. doi:10.1007/s40262-016-0383-6. PMID 27028535. S2CID 5078489.
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  30. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
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