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Identification
NameEnflurane
Accession NumberDB00228  (APRD00234)
Typesmall molecule
Groupsapproved
Description

An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-chloro-1,1,2-trifluoroethyl difluoromethyl etherNot AvailableNot Available
AlyraneNot AvailableNot Available
EfraneNot AvailableNot Available
EnfluranoSpanishINN
EnfluranumLatinINN
EthraneNot AvailableNot Available
MethylfluretherNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AlyraneBaxter
Compound 347Dexa Medica
EnduraneSingapore Pharmawealth Lifesciences
EnfluranCristália
EthraneAbbott
Brand mixturesNot Available
Categories
CAS number13838-16-9
WeightAverage: 184.492
Monoisotopic: 183.971433418
Chemical FormulaC3H2ClF5O
InChI KeyJPGQOUSTVILISH-UHFFFAOYSA-N
InChI
InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H
IUPAC Name
2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
SMILES
FC(F)OC(F)(F)C(F)Cl
Mass Specshow(7.54 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
IndicationUsed for the induction and maintenance of general anaesthesia during surgery and cesarean section and also used for analgesia during vaginal delivery.
PharmacodynamicsEnflurane is an extremely stable halogenated ether inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate. Enflurane induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. Induction of and recovery from anesthesia with enflurane are rapid. Enflurane may provide a mild stimulus to salivation or tracheobronchial secretions. Pharyngeal and laryngeal reflexes are readily obtunded. In the cardiovascular system, enflurane is a mild negative inotrope, causing a marked decrease in systemic vascular resistance, thus leading to a decrease in mean arterial pressure. This results in a reflex tachycardia. Enflurane also decreases coronary vascular resistance and sensitizes the myocardium to circulating catecholamines. Enflurane is a strong respiratory depressant. It decreases tidal volume but may increase respiratory rate. It also causes bronchodilatationa and inhibits pulmonary macrophage activity and mucociliary activity. Enflurane principle action in the CNS is general anaesthesia with little analgesic effect. It causes increased cerebral blood flow in concentrations and may induce tonic/clonic muscle activity and epileptiform EEG traces. It also causes a marked decrease in skeletal muscle tone. Actions in the genitourinary system include a decreased renal blood flow and glomerular filtration rate and the tone of pregnant uterus is decreased.
Mechanism of actionEnflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Enflurane 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. Enflurane also binds to and angonizes the GABA receptor, the large conductance Ca2+ activated potassium channel, the glycine receptor, and antagonizes the glutamate receptor receptor. These yield a decreased depolarization and therefore, tissue excitability which results in anesthesia.
AbsorptionRapidly absorbed into the circulation via the lungs.
Volume of distributionNot Available
Protein binding97%
Metabolism

2.4% of the dose is slowly metabolized hepatically via oxidation and dehalogenation (primarily through the actions of cytochrome P450 2E1). Leads to low levels of serum fluoride (15 µmol/L).

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLD50=5.4 ml/kg (oral, rat). Symptoms of acute overdose include nausea, vomiting, irritation to the eyes, skin and nose/throat, headache, dizziness, and drowsiness. Symptoms of chronic overdose include hypotension, cardiac arrhythmias, respiratory depression, and liver/kidney dysfunction.
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
  • Abbott laboratories hosp products div
  • Piramal critical care inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Dosage forms
FormRouteStrength
LiquidRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Ethrane inhalation0.55USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
boiling point56.5Terrell, R.C.; U.S. Patents 3,469,011; September 23,1969 and 3,527,813; September 8, 1970; both assigned to Air Reduction Company, Incorporated.
water solubility5620 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.10HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
water solubility3.90e+00 g/lALOGPS
logP2.24ALOGPS
logP2.8ChemAxon
logS-1.7ALOGPS
pKa (strongest basic)-5ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area9.23ChemAxon
rotatable bond count3ChemAxon
refractivity23.07ChemAxon
polarizability9.74ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Terrell, R.C.; U.S. Patents 3,469,011; September 23,1969 and 3,527,813; September 8,
1970; both assigned to Air Reduction Company, Incorporated.

General Reference
  1. Link
External Links
ResourceLink
KEGG DrugD00543
KEGG CompoundC07516
PubChem Compound3226
PubChem Substance46505314
ChemSpider3113
ChEBI4792
ChEMBLCHEMBL1257
Therapeutic Targets DatabaseDAP000799
PharmGKBPA449461
Drug Product Database778370
WikipediaEnflurane
ATC CodesN01AB04
AHFS Codes
  • 28:04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(64.9 KB)
Interactions
Drug Interactions
Drug
LabetalolMonitor arterial pressure closely
RotigotineRisk of sedation may increase with concomitant therapy. Monitor therapy closely.
Food InteractionsNot Available

Targets

1. 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)
  2. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. 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. Greenblatt EP, Meng X: Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors. Anesthesiology. 2001 Jun;94(6):1026-33. Pubmed

2. Glycine receptor (alpha-1/beta)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glycine receptor subunit alpha-1 P23415 Details
Glycine receptor subunit beta P48167 Details

References:

  1. 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
  2. ChEMBL Compound Report Card (Accessed December 2013)

3. Intermediate conductance calcium-activated potassium channel protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Intermediate conductance calcium-activated potassium channel protein 4 O15554 Details

References:

  1. Namba T, Ishii TM, Ikeda M, Hisano T, Itoh T, Hirota K, Adelman JP, Fukuda K: Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics. Eur J Pharmacol. 2000 Apr 28;395(2):95-101. 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. 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

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. Kosk-Kosicka D: Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. Adv Pharmacol. 1994;31:313-22. Pubmed
  2. Kosk-Kosicka D, Roszczynska G: Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. Anesthesiology. 1993 Oct;79(4):774-80. Pubmed

6. Glutamate receptor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor 1 P42261 Details

References:

  1. 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

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

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

Carriers

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

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Drug created on June 13, 2005 07:24 / Updated on April 16, 2014 14:53