|Systematic (IUPAC) name|
1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
|Mol. mass||184.5 g/mol|
| (what is this?)
Isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane) is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula. It is a racemic mixture of (R) and (S) optical isomers. Its use in human medicine is now starting to decline, being replaced with sevoflurane, desflurane and the intravenous anaesthetic propofol. Isoflurane is still frequently used for veterinary anaesthesia.
Isoflurane is always administered in conjunction with air and/or pure oxygen. Often nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane, its pungency can irritate the respiratory system, negating this theoretical advantage conferred by its physical properties. It is usually used to maintain a state of general anesthesia that has been induced with another drug, such as thiopentone or propofol. It vaporizes readily, but is a liquid at room temperature. It is completely nonflammable.
Physical properties 
|Boiling point (at 1 atm):||48.5 °C|
|Density (at 25 °C):||1.496 g/mL|
|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)|
|Blood:gas partition coefficient:||1.4|
|Oil:gas partition coefficient:||98|
Mechanism of action 
Similar to many general anesthetics, how isoflurane works remains incompletely understood. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamates and glycine receptors, but has different effects on each receptor. It inhibits glycine receptor activity, which decreases motor function. It increases receptor activity in the NMDA glutamate receptor subtype. Isoflurane inhibits conduction in activated potassium channels. Isoflurane also affects intracellular molecules. It activates calcium ATPase by increasing membrane fluidity. It binds to the D subunit of ATP synthase and NADH dehydrogenase.
Concerns have been raised as to the safety of certain general anesthetics, in particular ketamine and isoflurane in infants and young children due to significant neurodegeneration. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. This has led the FDA and other bodies to take steps to investigate these concerns.
Use with the elderly 
Concerns exist with regard to the relationship between administration of isoflurane and postoperative cognitive dysfunction (POCD), for which the elderly are especially vulnerable. Exposure of cultured human cells to isoflurane has been reported to induce apoptosis and accumulation and aggregation of amyloid beta protein, and may contribute to POCD, but this remains unknown. The study was based on in vitro research; further in vivo research is needed to determine the relevance of these findings in clinical practice and to improve the safety of anesthesia. An animal model has shown anesthesia with isoflurane increases amyloid pathology in mice models of Alzheimer's disease, and has been shown to induce cognitive decline in mice. Memory impairment following isoflurane anesthesia in mice can be prevented by pre-administering the GABA(A)α5 subunit inverse agonist L-655,708. It is not yet known if the drug can help prevent POCD in humans.
Biophysical studies using state-of-the-art 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. This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer’s disease".
- Mellon, RD.; Simone, AF.; Rappaport, BA. (Mar 2007). "Use of anesthetic agents in neonates and young children.". Anesth Analg 104 (3): 509–20. doi:10.1213/01.ane.0000255729.96438.b0. PMID 17312200.
- M. C. Lewis, I. Nevoa, M. A. Paniaguaa, A. Ben-Aric, E. Prettoa, S. Eisdorfera, E. Davidsona, I. Matotc, C. Eisdorfer (2007). "Uncomplicated general anesthesia in the elderly results in cognitive decline: Does cognitive decline predict morbidity and mortality?". Medical Hypotheses 68 (3): 484–492. doi:10.1016/j.mehy.2006.08.030. PMID 17141964.
- Z. Xie, Y. Dong, U. Maeda, R. D. Moir, W. Xia, D. J. Culley, G. Crosby, R. E. Tanzi (2007). "The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid β-Protein Accumulation". Journal of Neuroscience 27 (6): 1247–1254. doi:10.1523/JNEUROSCI.5320-06.2007. PMID 17287498.
- S. L. Bianchi, T. Tran, C. Liu, S. Lin, Y. Li, J. M. Keller, R. G. Eckenhoff, M. F. Eckenhoff (2007). "Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics". Neurobiology of Aging 28 (in press): 1002–10. doi:10.1016/j.neurobiolaging.2007.02.009. PMID 17346857.
- Saab, BJ; Maclean AJ, Kanisek M, Zurek AA, Martin LJ, Roder JC, Orser BA (November 2010). "Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708.". Anesthesiology 113 (5): 1061–71. doi:10.1097/ALN.0b013e3181f56228. PMID 20966663.
- Kuehn, BM. (Apr 2007). "Anesthesia-Alzheimer disease link probed". JAMA 297 (16): 1760. doi:10.1001/jama.297.16.1760. PMID 17456811.