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| Trade names | Forane, others |
| AHFS/Drugs.com | FDA Professional Drug Information |
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| Routes of administration | Respiratory |
| Drug class | Inhalational anesthetic |
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| Pharmacokinetic data | |
| Onset of action | 1.14±0.35 min to 50% steady-state.[6] |
| Elimination half-life | ~10 minutes[6] |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.043.528 |
| Chemical and physical data | |
| Formula | C3H2ClF5O |
| Molar mass | 184.49 g·mol−1 |
| 3D model (JSmol) | |
| Density | 1.496 g/cm3 [7] |
| Boiling point | 48.5 °C (119.3 °F) [7] |
| Solubility in water | 13.5 mM (at 25 °C (77 °F))[8] |
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Isoflurane, sold under the brand name Forane among others, is a halogenated ether used as a general anesthetic.[4][9] 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][10] Isoflurane is a inhalational anesthetic given via inhalation.[4]
Isoflurane was approved for medical use in the United States in 1979.[4][11] It is on the World Health Organization's List of Essential Medicines.[12]
Medical uses
Isoflurane is indicated for induction and maintenance of general anesthesia.[4]
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,[13] 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.[14][15][16]
Mechanism of action
Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.[17] 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.[18][19][20][21] It potentiates glycine receptor activity, which decreases motor function.[22] It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels.[23] 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.[24] 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.[25]
Adverse effects
Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat.[3] Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients.[16]
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]
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.[26] Whether these concerns occur in humans is unclear.[26]
Elderly
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.[27] This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer's disease".[28]
Anesthetic physical properties
Isoflurane has a Minimum alveolar concentration (MAC) of 1.15 vol %. The blood/gas partition coefficient is 1.4, and the oil/gas partition coefficient is 98.[citation needed] Its vapor pressure at 20 °C (68 °F) is 31.7 kilopascals (238 mmHg).[7]
It is administered as a racemic mixture of (R)- and (S)-optical isomers.[29] It is non-combustible but can give off irritable and toxic fumes when exposed to flame.[7]
History
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]
Environment
The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 (times greater than carbon dioxide) and yearly emissions as of 2015 were 880 tons.[32][needs update]
Veterinary use
Isoflurane is used for the induction and maintenance of general anesthesia in horses and dogs.[33][34][35][36][37] Used on Koalas.[38]
References
- ^ "Isoflurane Use During Pregnancy". Drugs.com. 2 September 2020. Retrieved 9 September 2020.
- ^ 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.
- ^ a b c d e "Isoflurane 100% Inhalation Vapour, Liquid - Summary of Product Characteristics (SmPC)". (emc). 29 October 2019. Retrieved 9 September 2020.
- ^ a b c d e f g "Forane- isoflurane inhalant". DailyMed. Retrieved 11 February 2022.
- ^ "Terrell- isoflurane liquid". DailyMed. 9 February 2023. Retrieved 4 October 2025.
- ^ a b Freiermuth D, Mets B, Bolliger D, Reuthebuch O, Doebele T, Scholz M, et al. (December 2016). "Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and Cardioprotective Effects During Cardiopulmonary Bypass". Journal of Cardiothoracic and Vascular Anesthesia. 30 (6): 1494–1501. doi:10.1053/j.jvca.2016.07.011. PMID 27692704.
- ^ a b c d "Isoflurane". PubChem. U.S. National Library of Medicine. Retrieved 7 April 2022.
- ^ Seto T, Mashimo T, Yoshiya I, Kanashiro M, Taniguchi Y (January 1992). "The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy". Journal of Pharmaceutical and Biomedical Analysis. 10 (1): 1–7. doi:10.1016/0731-7085(92)80003-6. PMID 1391078.
- ^ Aglio LS, Lekowski RW, Urman RD (2015). Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. p. 115. ISBN 978-1-107-68130-9. Archived from the original on 20 December 2016.
- ^ Kliegman R, Stanton B, St Geme J, Schor NF (2015). Nelson Textbook of Pediatrics (20 ed.). Elsevier Health Sciences. p. 420. ISBN 978-0-323-26352-8. Archived from the original on 20 December 2016.
- ^ "Forane: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 11 February 2022.
- ^ World Health Organization (2025). The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. doi:10.2471/B09474. hdl:10665/382243. License: CC BY-NC-SA 3.0 IGO.
- ^ 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 9 May 2016.
- ^ 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.
- ^ 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.
- ^ a b Hawkley TF, Preston M, Maani CV (2022). "Isoflurane". StatPearls. PMID 30422552.
- ^ "How does anesthesia work?". Scientific American. 7 February 2005. Archived from the original on 29 May 2016.
- ^ 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.
- ^ Jenkins A, Franks NP, Lieb WR (February 1999). "Effects of temperature and volatile anesthetics on GABA(A) receptors". Anesthesiology. 90 (2): 484–491. doi:10.1097/00000542-199902000-00024. PMID 9952156.
- ^ Lin LH, Chen LL, Zirrolli JA, Harris RA (November 1992). "General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium". The Journal of Pharmacology and Experimental Therapeutics. 263 (2): 569–578. doi:10.1016/S0022-3565(25)10387-X. PMID 1331405.
- ^ 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.
- ^ 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.
- ^ Buljubasic N, Rusch NJ, Marijic J, Kampine JP, Bosnjak ZJ (June 1992). "Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells". Anesthesiology. 76 (6): 990–998. doi:10.1097/00000542-199206000-00020. PMID 1318010.
- ^ Franks JJ, Horn JL, Janicki PK, Singh G (January 1995). "Halothane, isoflurane, xenon, and nitrous oxide inhibit calcium ATPase pump activity in rat brain synaptic plasma membranes". Anesthesiology. 82 (1): 108–117. doi:10.1097/00000542-199501000-00015. PMID 7832292. S2CID 26993898.
- ^ Weis F, Beiras-Fernandez A, Hauer D, Hornuss C, Sodian R, Kreth S, et al. (August 2010). "Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery". British Journal of Anaesthesia. 105 (2): 139–144. doi:10.1093/bja/aeq117. PMID 20525978.
- ^ 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 9 March 2009.
- ^ Mandal, et al. (April 2009). "Isoflurane and desflurane at clinically relevant concentrations induce amyloid b-peptide oligomerization: An NMR study". Biochemical and Biophysical Research Communications. 379 (3): 716–720. Bibcode:2009BBRC..379..716M. doi:10.1016/j.bbrc.2008.12.092. PMID 19116131.
- ^ Kuehn BM (April 2007). "Anesthesia-Alzheimer disease link probed". JAMA. 297 (16): 1760. doi:10.1001/jama.297.16.1760. PMID 17456811.
- ^ Bu W, Pereira LM, Eckenhoff RG, Yuki K (6 May 2014). "Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1". PLOS ONE. 9 (5) e96649. Bibcode:2014PLoSO...996649B. doi:10.1371/journal.pone.0096649. PMC 4011845. PMID 24801074.
- ^ Terrell RC (March 2008). "The invention and development of enflurane, isoflurane, sevoflurane, and desflurane". Anesthesiology. 108 (3): 531–533. doi:10.1097/ALN.0b013e31816499cc. PMID 18292690.
- ^ Calvey TN (August 1995). "Isomerism and anaesthetic drugs". Acta Anaesthesiologica Scandinavica. Supplementum. 106: 83–90. doi:10.1111/j.1399-6576.1995.tb04316.x. PMID 8533553. S2CID 24183480.
- ^ Vollmer MK, Rhee TS, Rigby M, Hofstetter D, Hill M, Schoenenberger F, et al. (2015). "Modern inhalation anesthetics: Potent greenhouse gases in the global atmosphere". Geophysical Research Letters. 42 (5): 1606–1611. Bibcode:2015GeoRL..42.1606V. doi:10.1002/2014GL062785.
- ^ "Isosol- isoflurane liquid". DailyMed. 2 February 2023. Retrieved 4 October 2025.
- ^ "Isospire- isoflurane liquid". DailyMed. 13 December 2023. Retrieved 4 October 2025.
- ^ "Fluriso- isoflurane liquid". DailyMed. 14 February 2023. Retrieved 4 October 2025.
- ^ Ludders JW (March 1992). "Advantages and guidelines for using isoflurane". The Veterinary Clinics of North America. Small Animal Practice. 22 (2): 328–331. doi:10.1016/s0195-5616(92)50626-x. PMID 1585568.
- ^ "Isoflurane-Vet 100% w/w Inhalation vapour, liquid". www.noahcompendium.co.uk. Retrieved 7 April 2022.
- ^ "Animals with Cameras". www.pbs.org. Retrieved 14 January 2026.
External links
- U.S. patent 3,535,388 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
- U.S. patent 3,535,425 - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether as an anesthetic agent
- 5-HT3 receptor positive allosteric modulators
- Difluoromethoxy compounds
- Ethers
- Fluranes
- GABAA receptor positive allosteric modulators
- General anesthetics
- Glycine receptor agonists
- Nicotinic antagonists
- NMDA receptor antagonists
- Organochlorides
- Organofluorides
- Psychoplastogens
- Trifluoroethyl compounds
- World Health Organization essential medicines
