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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
1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propaneNot AvailableNot Available
SevofluranNot AvailableNot Available
SevofluraneNot AvailableNot Available
SevofluranoSpanishINN
SevofluranumLatinINN
SaltsNot Available
Brand names
NameCompany
SevoraneNot Available
SojournNot Available
UltaneNot Available
Brand mixturesNot Available
Categories
CAS number28523-86-6
WeightAverage: 200.0548
Monoisotopic: 200.007212153
Chemical FormulaC4H3F7O
InChI KeyDFEYYRMXOJXZRJ-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
Not Available
FluorideDetails
Sevoflurane
Not Available
Carbon dioxideDetails
Sevoflurane
Not Available
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

Targets

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)

Enzymes

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

Carriers

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

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