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Identification
NameEnflurane
Accession NumberDB00228  (APRD00234)
TypeSmall Molecule
GroupsApproved, Vet Approved
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
2-chloro-1,1,2-trifluoroethyl difluoromethyl ether
Alyrane
Efrane
Enflurane
Enflurano
Enfluranum
Ethrane
Methylflurether
External Identifiers
  • Anesthetic 347
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Enfluraneliquid99.9 %inhalationAbbvie Corporation1993-12-312012-11-02Canada
Ethrane Liq Inhliquid100 %inhalationOhmeda Pharmaceutical Products, Division Of Boc Canada Limited1996-09-181997-08-25Canada
Ethrane Liquid Inhliquid100 %inhalationBaxter Corporation1997-02-202004-08-05Canada
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AlyraneBaxter
Compound 347Dexa Medica
EnduraneSingapore Pharmawealth Lifesciences
EnfluranCristália
EthraneAbbott
Brand mixturesNot Available
SaltsNot Available
Categories
UNII91I69L5AY5
CAS number13838-16-9
WeightAverage: 184.492
Monoisotopic: 183.971433418
Chemical FormulaC3H2ClF5O
InChI KeyInChIKey=JPGQOUSTVILISH-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as halomethanes. These are organic compounds in which at least one of the four hydrogen atoms of methane (CH4) are replaced by halogen atoms.
KingdomOrganic compounds
Super ClassOrganohalogen compounds
ClassAlkyl halides
Sub ClassHalomethanes
Direct ParentHalomethanes
Alternative Parents
Substituents
  • Halomethane
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organochloride
  • Alkyl fluoride
  • Alkyl chloride
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.994
Caco-2 permeable+0.6125
P-glycoprotein substrateNon-substrate0.8919
P-glycoprotein inhibitor INon-inhibitor0.9553
P-glycoprotein inhibitor IINon-inhibitor0.9297
Renal organic cation transporterNon-inhibitor0.9293
CYP450 2C9 substrateNon-substrate0.8407
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7179
CYP450 1A2 substrateNon-inhibitor0.5701
CYP450 2C9 inhibitorNon-inhibitor0.8112
CYP450 2D6 inhibitorNon-inhibitor0.9408
CYP450 2C19 inhibitorNon-inhibitor0.5794
CYP450 3A4 inhibitorNon-inhibitor0.9604
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8702
Ames testNon AMES toxic0.9132
CarcinogenicityCarcinogens 0.7574
BiodegradationNot ready biodegradable0.9642
Rat acute toxicity1.3804 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9576
hERG inhibition (predictor II)Non-inhibitor0.9032
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Abbott laboratories hosp products div
  • Piramal critical care inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Dosage forms
FormRouteStrength
Liquidinhalation99.9 %
Liquidinhalation100 %
Prices
Unit descriptionCostUnit
Ethrane inhalation0.55USD ml
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 Solubility3.9 mg/mLALOGPS
logP2.24ALOGPS
logP2.8ChemAxon
logS-1.7ALOGPS
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity23.07 m3·mol-1ChemAxon
Polarizability9.74 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.54 KB)
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-zd00000000-03817aefdcc06ee54c49View in MoNA
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 References
  1. Link [Link]
External Links
ATC CodesN01AB04
AHFS Codes
  • 28:04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (64.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein group
Organism
Human
Pharmacological action
yes
Actions
positive allosteric modulator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Components:
NameUniProt IDDetails
Gamma-aminobutyric acid receptor subunit alpha-1P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3P28472 Details
Gamma-aminobutyric acid receptor subunit deltaO14764 Details
Gamma-aminobutyric acid receptor subunit epsilonP78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3Q99928 Details
Gamma-aminobutyric acid receptor subunit piO00591 Details
Gamma-aminobutyric acid receptor subunit thetaQ9UN88 Details
References
  1. Franks NP: Molecular targets underlying general anaesthesia. Br J Pharmacol. 2006 Jan;147 Suppl 1:S72-81. [PubMed:16402123 ]
  2. 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:16973644 ]
  3. Greenblatt EP, Meng X: Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors. Anesthesiology. 2001 Jun;94(6):1026-33. [PubMed:11465594 ]
  4. ChEMBL Compound Report Card [Link]
Kind
Protein group
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Components:
NameUniProt IDDetails
Glycine receptor subunit alpha-1P23415 Details
Glycine receptor subunit betaP48167 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:16973644 ]
  2. ChEMBL Compound Report Card [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Protein phosphatase binding
Specific Function:
Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMe...
Gene Name:
KCNN4
Uniprot ID:
O15554
Molecular Weight:
47695.12 Da
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:10794813 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inducer
General Function:
Voltage-gated potassium channel activity
Specific Function:
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which ...
Gene Name:
KCNA1
Uniprot ID:
Q09470
Molecular Weight:
56465.01 Da
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. doi: 10.1179/174313209X393546. [PubMed:19298752 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Signal transducer activity
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name:
ATP2C1
Uniprot ID:
P98194
Molecular Weight:
100576.42 Da
References
  1. Kosk-Kosicka D: Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. Adv Pharmacol. 1994;31:313-22. [PubMed:7873420 ]
  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:8214757 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Pdz domain binding
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inacti...
Gene Name:
GRIA1
Uniprot ID:
P42261
Molecular Weight:
101505.245 Da
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:8786535 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Transporter activity
Specific Function:
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked toget...
Gene Name:
ATP5D
Uniprot ID:
P30049
Molecular Weight:
17489.755 Da
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:8214757 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
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:15791110 ]
  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:15449957 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on April 16, 2014 14:53