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Trade namesForane, others
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  • (RS)-2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane
    (RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
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ECHA InfoCard100.043.528 Edit this at Wikidata
Chemical and physical data
Molar mass184.49 g·mol−1
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  • FC(F)(F)C(Cl)OC(F)F
  • InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H checkY
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Isoflurane, sold under the brand name Forane among others, is a general anesthetic.[4] It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane.[3][5] Isoflurane is given via inhalation.[4]

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat.[3] Serious side effects can include malignant hyperthermia or high blood potassium.[4] It should not be used in patients with a history of malignant hyperthermia in either themselves or their family members.[3] It is unknown if its use during pregnancy is safe for the fetus, but use during a cesarean section appears to be safe.[3][4] Isoflurane is a halogenated ether.[6]

Isoflurane was approved for medical use in the United States in 1979.[4][7] It is on the World Health Organization's List of Essential Medicines.[8][9]

Medical uses

Isoflurane is always administered in conjunction with air or pure oxygen. Often, nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane,[10] its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. Thus, it is mostly used in general anesthesia as a maintenance agent after induction of general anesthesia with an intravenous agent such as thiopentone or propofol.[11][12][13]

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.[14] Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors.[15][16][17][18] It potentiates glycine receptor activity, which decreases motor function.[19] It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels.[20] Isoflurane also affects intracellular molecules. It inhibits plasma membrane calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of Ca2+ (calcium ions) out across the membrane, this in turn affects neuron depolarization.[21][22] It binds to the D subunit of ATP synthase and NADH dehydrogenase.

General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness.[23]

Adverse effects

Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients.[13]

Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam.[24] Whether these concerns occur in humans is unclear.[24]


Biophysical studies using NMR spectroscopy has provided molecular details of how inhaled anesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induce aggregation.[25] This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer's disease".[26]

Physical properties

Molecular weight 184.5g/mol[27]
Boiling point (at 1 atm): 48.5 °C[27]
Density (at 25 °C): 1.496 g/mL[27]
MAC : 1.15 vol %
Vapor pressure: 238 mmHg 31.7 kPa (at 20 °C)
295 mmHg 39.3 kPa (at 25 °C)
367 mmHg 48.9 kPa (at 30 °C)
450 mmHg 60.0 kPa (at 35 °C)[27]
Water solubility 13.5 mM (at 25 °C)[28]
Blood:gas partition coefficient: 1.4
Oil:gas partition coefficient: 98

It is administered as a racemic mixture of (R)- and (S)-optical isomers.[29] Isoflurane has a boiling point of 48.5 - 49 °C (119 - 120 °F).[27] It is non-combustible but can give off irritable and toxic fumes when exposed to flame.[27]


Together with enflurane and halothane, Isoflurane began to replace the flammable ethers used in the pioneer days of surgery; this shift began in the 1940s to the 1950s.[30] Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula.[31]


The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 and the yearly emissions add up to 880 tons.[32]

Veterinary use

Isoflurane is frequently used for veterinary anaesthesia.[33][34]


  1. ^ "Isoflurane Use During Pregnancy". 2 September 2020. Retrieved 9 September 2020.
  2. ^ Anvisa (2023-03-31). "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 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ a b c d e "Isoflurane 100% Inhalation Vapour, Liquid - Summary of Product Characteristics (SmPC)". (emc). 29 October 2019. Retrieved 9 September 2020.
  4. ^ a b c d e f "Forane- isoflurane inhalant". DailyMed. Retrieved 11 February 2022.
  5. ^ Kliegman R, Stanton B, St Geme J, Schor NF (2015). Nelson Textbook of Pediatrics (20 ed.). Elsevier Health Sciences. p. 420. ISBN 9780323263528. Archived from the original on 2016-12-20.
  6. ^ Aglio LS, Lekowski RW, Urman RD (2015). Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. p. 115. ISBN 9781107681309. Archived from the original on 2016-12-20.
  7. ^ "Forane: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 11 February 2022.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  10. ^ Niedermeyer E, da Silva FH (2005). Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins. p. 1156. ISBN 978-0-7817-5126-1. Archived from the original on 2016-05-09.
  11. ^ Pauca AL, Dripps RD (July 1973). "Clinical experience with isoflurane (Forane): preliminary communication". British Journal of Anaesthesia. 45 (7): 697–703. doi:10.1093/bja/45.7.697. PMID 4730162.
  12. ^ Chen Z (August 2004). "The effects of isoflurane and propofol on intraoperative neurophysiological monitoring during spinal surgery". Journal of Clinical Monitoring and Computing. 18 (4): 303–308. doi:10.1007/s10877-005-5097-5. PMID 15779842. S2CID 195331061.
  13. ^ a b Hawkley TF, Preston M, Maani CV (2022). "Isoflurane". StatPearls. PMID 30422552.
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  15. ^ Jones MV, Brooks PA, Harrison NL (April 1992). "Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics". The Journal of Physiology. 449: 279–293. doi:10.1113/jphysiol.1992.sp019086. PMC 1176079. PMID 1326046.
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  18. ^ Krasowski MD, Harrison NL (February 2000). "The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations". British Journal of Pharmacology. 129 (4): 731–743. doi:10.1038/sj.bjp.0703087. PMC 1571881. PMID 10683198.
  19. ^ Grasshoff C, Antkowiak B (November 2006). "Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats". British Journal of Anaesthesia. 97 (5): 687–694. doi:10.1093/bja/ael239. PMID 16973644. S2CID 14269792.
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  24. ^ a b Mellon RD, Simone AF, Rappaport BA (March 2007). "Use of anesthetic agents in neonates and young children". Anesthesia and Analgesia. 104 (3): 509–520. doi:10.1213/01.ane.0000255729.96438.b0. PMID 17312200. S2CID 43818997. Archived from the original on 2009-03-09.
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