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Identification
Name Enflurane
Accession Number DB00228 (APRD00234)
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Anesthetic 347
Anesthetic Compound No. 347
Compound 347
Enflurano [INN-Spanish]
Enfluranum [INN-Latin]
Methylflurether
Ohio 347
Salts Not Available
Brand names
Name Company
Alyrane
Efrane
Ethrane
Brand mixtures Not Available
Categories
  • Anesthetics, Inhalation
  • General Anesthetics
CAS number 13838-16-9
Weight Average: 184.492
Monoisotopic: 183.971433418
Chemical Formula C3H2ClF5O
InChI Key InChIKey=JPGQOUSTVILISH-UHFFFAOYSA-N
InChI
InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H
Plain Text
IUPAC Name
2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
SMILES
FC(F)OC(F)(F)C(F)Cl
Plain Text
Mass Spec show (7.54 KB)
Taxonomy
Kingdom Organic
Classes
  • Carboxylic Acids and Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Alkyl Halides
  • Ethers
Pharmacology
Indication Used for the induction and maintenance of general anaesthesia during surgery and cesarean section and also used for analgesia during vaginal delivery.
Pharmacodynamics Enflurane 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 action Enflurane 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.
Absorption Rapidly absorbed into the circulation via the lungs.
Volume of distribution Not Available
Protein binding 97%
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 elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity LD50=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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories hosp products div
  • Piramal critical care inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Dosage forms
Form Route Strength
Liquid Respiratory (inhalation)
Prices
Unit description Cost Unit
Ethrane inhalation 0.55 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
boiling point 56 °C Not Available
water solubility 5620 mg/L (at 37 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 2.10 HANSCH,C & LEO,AJ (1985)
Predicted Properties
Property Value Source
water solubility 3.90e+00 g/l ALOGPS
logP 2.24 ALOGPS
logP 2.8 ChemAxon
logS -1.7 ALOGPS
pKa (strongest basic) -5 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 9.23 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 23.07 ChemAxon
polarizability 9.74 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00543 Link_out
KEGG Compound C07516 Link_out
PubChem Compound 3226 Link_out
PubChem Substance 46505314 Link_out
ChemSpider 3113 Link_out
ChEBI 4792 Link_out
ChEMBL 4792 Link_out
Therapeutic Targets Database DAP000799 Link_out
PharmGKB PA449461 Link_out
Drug Product Database 778370 Link_out
Wikipedia http://en.wikipedia.org/wiki/Enflurane Link_out
ATC Codes
  • N01AB04
AHFS Codes
  • 28:04.92
PDB Entries Not Available
FDA label Not Available
MSDS show (64.9 KB)
Interactions
Drug Interactions
Drug Interaction
Labetalol Monitor arterial pressure closely
Food Interactions Not Available
Targets

1. Calcium-activated potassium channel subunit alpha 1

Pharmacological action: yes
Actions: inhibitor

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)

Organism class: human
UniProt ID: Q12791 Link_out
Gene: KCNMA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Antkowiak B, Kirschfeld K: Enflurane is a potent inhibitor of high conductance Ca(2+)-activated K+ channels of Chara australis. FEBS Lett. 1992 Nov 30;313(3):281-4. Pubmed

2. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: agonist

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. 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

3. Glutamate receptor 1

Pharmacological action: yes
Actions: antagonist

L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists

Organism class: human
UniProt ID: P42261 Link_out
Gene: GRIA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Glycine receptor subunit alpha-1

Pharmacological action: yes
Actions: agonist

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)

Organism class: human
UniProt ID: P23415 Link_out
Gene: GLRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Potassium voltage-gated channel subfamily A member 1

Pharmacological action: yes
Actions: inducer

Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient

Organism class: human
UniProt ID: Q09470 Link_out
Gene: KCNA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Calcium-transporting ATPase type 2C member 1

Pharmacological action: yes
Actions: inhibitor

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium

Organism class: human
UniProt ID: P98194 Link_out
Gene: ATP2C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

7. ATP synthase delta chain, mitochondrial

Pharmacological action: unknown
Actions: other/unknown

Produces ATP from ADP in the presence of a proton gradient across the membrane

Organism class: human
UniProt ID: P30049 Link_out
Gene: ATP5D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. NADH-ubiquinone oxidoreductase chain 1

Pharmacological action: unknown
Actions: unknown
Organism class: human
UniProt ID: P03886 Link_out
Gene: MT-ND1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2E1

Actions: substrate

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

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19