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Identification
NameSevoflurane
Accession NumberDB01236  (APRD00219)
Typesmall molecule
Groupsapproved
Description

Sevoflurane (2,2,2-trifluoro-1-[trifluoromethyl]ethyl fluoromethyl ether), also called fluoromethyl, is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
SevofluranNot AvailableNot Available
SevofluranoSpanishINN
SevofluranumLatinINN
SaltsNot Available
Brand names
NameCompany
SevoraneNot Available
UltaneNot Available
Brand mixturesNot Available
Categories
CAS number28523-86-6
WeightAverage: 200.0548
Monoisotopic: 200.007212153
Chemical FormulaC4H3F7O
InChI KeyInChIKey=DFEYYRMXOJXZRJ-UHFFFAOYSA-N
InChI
InChI=1S/C4H3F7O/c5-1-12-2(3(6,7)8)4(9,10)11/h2H,1H2
IUPAC Name
1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane
SMILES
FCOC(C(F)(F)F)C(F)(F)F
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsEthers; Organofluorides; Alkyl Fluorides
Substituentsorganofluoride; organohalogen; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationUsed for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.
PharmacodynamicsSevoflurane (also called fluoromethyl) is a halogenated ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. It is often administered in nitrous oxide and pure oxygen. After desflurane it is the volatile anesthetic with the fastest onset and offset. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.
Mechanism of actionSevoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Sevoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase and also binds to the GABA receptor, the large conductance Ca2+ activated potassium channel, the glutamate receptor, and the glycine receptor.
AbsorptionRapidly absorbed into circulation via the lungs, however solubility in the blood is low.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Relatively little biotransformation, only 5% is metabolized by cytochrome P450 CYP2E1 to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. No other metabolic pathways have been identified for sevoflurane.

SubstrateEnzymesProduct
Sevoflurane
    FluorideDetails
    Sevoflurane
      Carbon dioxideDetails
      Sevoflurane
        HexafluoroisopropanolDetails
        Route of eliminationThe low solubility of sevoflurane facilitates rapid elimination via the lungs. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized. Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride.
        Half life15-23 hours
        ClearanceNot Available
        ToxicityLC50=49881 ppm/hr (rat), LD50=10.8 g/kg (rat)
        Affected organisms
        • Humans and other mammals
        PathwaysNot Available
        SNP Mediated EffectsNot Available
        SNP Mediated Adverse Drug ReactionsNot Available
        ADMET
        Predicted ADMET features
        Property Value Probability
        Human Intestinal Absorption + 0.9963
        Blood Brain Barrier + 0.9941
        Caco-2 permeable + 0.6134
        P-glycoprotein substrate Non-substrate 0.8839
        P-glycoprotein inhibitor I Non-inhibitor 0.8807
        P-glycoprotein inhibitor II Non-inhibitor 0.5436
        Renal organic cation transporter Non-inhibitor 0.8649
        CYP450 2C9 substrate Non-substrate 0.9039
        CYP450 2D6 substrate Non-substrate 0.9116
        CYP450 3A4 substrate Non-substrate 0.6876
        CYP450 1A2 substrate Inhibitor 0.5254
        CYP450 2C9 substrate Non-inhibitor 0.7941
        CYP450 2D6 substrate Non-inhibitor 0.9114
        CYP450 2C19 substrate Inhibitor 0.5569
        CYP450 3A4 substrate Non-inhibitor 0.9148
        CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7006
        Ames test AMES toxic 0.5082
        Carcinogenicity Carcinogens 0.7014
        Biodegradation Not ready biodegradable 0.8564
        Rat acute toxicity 1.3361 LD50, mol/kg Not applicable
        hERG inhibition (predictor I) Weak inhibitor 0.9485
        hERG inhibition (predictor II) Non-inhibitor 0.8685
        Pharmacoeconomics
        Manufacturers
        • Baxter healthcare corp
        • Halocarbon products corp
        • Piramal critical care inc
        • Abbott laboratories
        Packagers
        Dosage forms
        FormRouteStrength
        LiquidRespiratory (inhalation)
        Prices
        Unit descriptionCostUnit
        Ultane 250 ml pen bottle1.16USDml
        Sojourn inhalation liquid0.99USDml
        Sevoflurane inhalation liquid0.89USDml
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents
        CountryPatent NumberApprovedExpires (estimated)
        United States60746681998-07-092018-07-09
        United States59901761997-01-272017-01-27
        Properties
        Stateliquid
        Experimental Properties
        PropertyValueSource
        melting point< 25 °CPhysProp
        boiling point58.5 °CPhysProp
        water solubilityVery slightly solubleNot Available
        logP2.4Not Available
        Predicted Properties
        PropertyValueSource
        water solubility1.48e+00 g/lALOGPS
        logP2.44ALOGPS
        logP2.27ChemAxon
        logS-2.1ALOGPS
        pKa (strongest acidic)15.07ChemAxon
        pKa (strongest basic)-4.5ChemAxon
        physiological charge0ChemAxon
        hydrogen acceptor count1ChemAxon
        hydrogen donor count0ChemAxon
        polar surface area9.23ChemAxon
        rotatable bond count4ChemAxon
        refractivity23.3ChemAxon
        polarizability9.83ChemAxon
        number of rings0ChemAxon
        bioavailability1ChemAxon
        rule of fiveYesChemAxon
        Ghose filterNoChemAxon
        Veber's ruleYesChemAxon
        MDDR-like ruleNoChemAxon
        Spectra
        SpectraNot Available
        References
        Synthesis Reference

        Ross C. Terrell, “Method for the preparation of sevoflurane.” U.S. Patent US5969193, issued December, 1979.

        US5969193
        General ReferenceNot Available
        External Links
        ResourceLink
        KEGG DrugD00547
        KEGG CompoundC07520
        PubChem Compound5206
        PubChem Substance46508591
        ChemSpider5017
        ChEBI9130
        ChEMBLCHEMBL1200694
        Therapeutic Targets DatabaseDAP000694
        PharmGKBPA451341
        Drug Product Database2172763
        RxListhttp://www.rxlist.com/cgi/generic/sevoflurane.htm
        Drugs.comhttp://www.drugs.com/cdi/sevoflurane.html
        WikipediaSevoflurane
        ATC CodesN01AB08
        AHFS Codes
        • 28:04.00
        PDB EntriesNot Available
        FDA labelshow(188 KB)
        MSDSshow(49.5 KB)
        Interactions
        Drug InteractionsNot Available
        Food InteractionsNot Available

        1. Gamma-aminobutyric acid receptor subunit alpha-1

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: agonist

        Components

        Name UniProt ID Details
        Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        2. Glycine receptor subunit alpha-1

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: agonist

        Components

        Name UniProt ID Details
        Glycine receptor subunit alpha-1 P23415 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        3. Glutamate receptor 1

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: antagonist

        Components

        Name UniProt ID Details
        Glutamate receptor 1 P42261 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        4. Potassium voltage-gated channel subfamily A member 1

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: inducer

        Components

        Name UniProt ID Details
        Potassium voltage-gated channel subfamily A member 1 Q09470 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        5. Calcium-transporting ATPase type 2C member 1

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Calcium-transporting ATPase type 2C member 1 P98194 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        6. ATP synthase subunit delta, mitochondrial

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: other/unknown

        Components

        Name UniProt ID Details
        ATP synthase subunit delta, mitochondrial P30049 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        7. NADH-ubiquinone oxidoreductase chain 1

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: unknown

        Components

        Name UniProt ID Details
        NADH-ubiquinone oxidoreductase chain 1 P03886 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

        8. GABA-A receptor (anion channel)

        Kind: protein group

        Organism: Human

        Pharmacological action: yes

        Actions: positive allosteric modulator

        Components

        Name UniProt ID Details
        Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
        Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
        Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
        Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
        Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
        Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
        Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
        Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
        Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
        Gamma-aminobutyric acid receptor subunit delta O14764 Details
        Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
        Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
        Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
        Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
        Gamma-aminobutyric acid receptor subunit pi O00591 Details
        Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

        References:

        1. ChEMBL Compound Report Card (Accessed December 2013)

        1. Cytochrome P450 2E1

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2E1 P05181 Details

        References:

        1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        2. Cytochrome P450 2A6

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2A6 P11509 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        3. Cytochrome P450 2B6

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2B6 P20813 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        4. Cytochrome P450 3A4

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A4 P08684 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        1. Serum albumin

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Components

        Name UniProt ID Details
        Serum albumin P02768 Details

        References:

        1. Sawas AH, Pentyala SN, Rebecchi MJ: Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions. Biochemistry. 2004 Oct 5;43(39):12675-85. Pubmed

        Comments
        Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13