Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameIsoflurane
Accession NumberDB00753  (APRD00212)
Typesmall molecule
Groupsapproved
Description

A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
IsofluraneNot AvailableINN, BAN, USAN, JAN
IsofluranumLatinINN
SaltsNot Available
Brand names
NameCompany
AerraneNot Available
EthaneNot Available
ForaneNot Available
ForeneNot Available
Brand mixturesNot Available
Categories
CAS number26675-46-7
WeightAverage: 184.492
Monoisotopic: 183.971433418
Chemical FormulaC3H2ClF5O
InChI KeyInChIKey=PIWKPBJCKXDKJR-UHFFFAOYSA-N
InChI
InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H
IUPAC Name
2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane
SMILES
FC(F)OC(Cl)C(F)(F)F
Mass Specshow(7.33 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsEthers; Organofluorides; Organochlorides; Alkyl Fluorides; Alkyl Chlorides
Substituentsorganofluoride; organochloride; organohalogen; alkyl halide; alkyl fluoride; alkyl chloride
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor induction and maintenance of general anesthesia.
PharmacodynamicsIsoflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. 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 actionIsoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Isoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. Also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Isoflurane also binds to the GABA receptor, the large conductance Ca2+ activated potassium channel, the glutamate receptor and the glycine receptor.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Minimal

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLC50=15300 ppm/3 hrs (inhalation by 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 + 1.0
Blood Brain Barrier + 0.994
Caco-2 permeable + 0.6125
P-glycoprotein substrate Non-substrate 0.8919
P-glycoprotein inhibitor I Non-inhibitor 0.9553
P-glycoprotein inhibitor II Non-inhibitor 0.9297
Renal organic cation transporter Non-inhibitor 0.9293
CYP450 2C9 substrate Non-substrate 0.8407
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7179
CYP450 1A2 substrate Non-inhibitor 0.5701
CYP450 2C9 substrate Non-inhibitor 0.8112
CYP450 2D6 substrate Non-inhibitor 0.9408
CYP450 2C19 substrate Non-inhibitor 0.5794
CYP450 3A4 substrate Non-inhibitor 0.9604
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8702
Ames test Non AMES toxic 0.9132
Carcinogenicity Carcinogens 0.7574
Biodegradation Not ready biodegradable 0.9642
Rat acute toxicity 1.3804 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9576
hERG inhibition (predictor II) Non-inhibitor 0.9032
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Halocarbon products corp
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Piramal critical care inc
  • Rhodia ltd
Packagers
Dosage forms
FormRouteStrength
LiquidRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Forane liquid0.24USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point48.5 °CPhysProp
boiling point48.5 °CPhysProp
water solubility4470 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.06HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility3.56e+00 g/lALOGPS
logP2.3ALOGPS
logP2.84ChemAxon
logS-1.7ALOGPS
pKa (strongest basic)-4.7ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area9.23ChemAxon
rotatable bond count3ChemAxon
refractivity23.04ChemAxon
polarizability9.73ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Leonid A. Rozov, Fernando Quiroz, Gerald G. Vernice, “Preparation of isoflurane.” U.S. Patent US5416244, issued March, 1973.

US5416244
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00545
KEGG CompoundC07518
PubChem Compound3763
PubChem Substance46505880
ChemSpider3631
ChEBI6015
ChEMBLCHEMBL1256
Therapeutic Targets DatabaseDAP001033
PharmGKBPA450106
HETICF
Drug Product Database2241315
RxListhttp://www.rxlist.com/cgi/generic3/isoflurane.htm
WikipediaIsoflurane
ATC CodesN01AB06
AHFS Codes
  • 28:04.00
  • 28:04.92
PDB EntriesNot Available
FDA labelshow(99.6 KB)
MSDSshow(37 KB)
Interactions
Drug Interactions
Drug
LabetalolMonitor arterial pressure closely
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
  3. McCracken ML, Borghese CM, Trudell JR, Harris RA: A Transmembrane Amino Acid in the GABAA Receptor {beta}2 Subunit Critical for the Actions of Alcohols and Anesthetics. J Pharmacol Exp Ther. 2010 Sep 8. Pubmed
  4. Seo K, Seino H, Yoshikawa H, Petrenko AB, Baba H, Fujiwara N, Someya G, Kawano Y, Maeda T, Matsuda M, Kanematsu T, Hirata M: Genetic reduction of GABA receptor gamma2 subunit expression potentiates the immobilizing action of isoflurane. Neurosci Lett. 2010 Mar 12;472(1):1-4. Epub 2010 Jan 25. Pubmed

2. 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
  3. Kosk-Kosicka D, Roszczynska G: Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. Anesthesiology. 1993 Oct;79(4):774-80. Pubmed

3. 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. Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. Epub 2006 Sep 13. Pubmed

4. Glutamate receptor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor 1 P42261 Details

References:

  1. Guo L, Wang Y: Glutamate stimulates glutamate receptor interacting protein 1 degradation by ubiquitin-proteasome system to regulate surface expression of GluR2. Neuroscience. 2007 Mar 2;145(1):100-9. Epub 2007 Jan 3. Pubmed
  2. Dildy-Mayfield JE, Eger EI 2nd, Harris RA: Anesthetics produce subunit-selective actions on glutamate receptors. J Pharmacol Exp Ther. 1996 Mar;276(3):1058-65. Pubmed

5. 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
  3. Matchett GA, Allard MW, Martin RD, Zhang JH: Neuroprotective effect of volatile anesthetic agents: molecular mechanisms. Neurol Res. 2009 Mar;31(2):128-34. Pubmed

6. ATP synthase subunit delta, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: 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. Calmodulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Calmodulin P62158 Details

References:

  1. Fan RS, Jacamo RO, Jiang X, Sinnett-Smith J, Rozengurt E: G protein-coupled receptor activation rapidly stimulates focal adhesion kinase phosphorylation at Ser-843. Mediation by Ca2+, calmodulin, and Ca2+/calmodulin-dependent kinase II. J Biol Chem. 2005 Jun 24;280(25):24212-20. Epub 2005 Apr 21. Pubmed
  2. Bickler PE, Zhan X, Fahlman CS: Isoflurane preconditions hippocampal neurons against oxygen-glucose deprivation: role of intracellular Ca2+ and mitogen-activated protein kinase signaling. Anesthesiology. 2005 Sep;103(3):532-9. Pubmed
  3. Sazonova OV, Blishchenko EY, Tolmazova AG, Khachin DP, Leontiev KV, Karelin AA, Ivanov VT: Stimulation of fibroblast proliferation by neokyotorphin requires Ca influx and activation of PKA, CaMK II and MAPK/ERK. FEBS J. 2007 Jan;274(2):474-84. 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 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

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

3. NADH-ubiquinone oxidoreductase chain 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

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
  3. Hanley PJ, Ray J, Brandt U, Daut J: Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol. 2002 Nov 1;544(Pt 3):687-93. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Liu R, Eckenhoff RG: Weak polar interactions confer albumin binding site selectivity for haloether anesthetics. Anesthesiology. 2005 Apr;102(4):799-805. Pubmed
  2. 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 17:12