Enflurane

Enflurane

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
ATC code	N01AB04 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)
Pharmacokinetic data
Protein binding	97%
Identifiers
IUPAC name (RS)-2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
CAS Number	13838-16-9 Y
PubChem CID	3226
IUPHAR/BPS	7175
DrugBank	DB00228 Y
ChemSpider	3113 Y
UNII	91I69L5AY5
KEGG	D00543 Y
ChEBI	CHEBI:4792 Y
ChEMBL	ChEMBL1257 Y
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C3H2ClF5O
Molar mass	184.49 g·mol−1
3D model (JSmol)	Interactive image
SMILES FC(Cl)C(F)(F)OC(F)F
InChI InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H Y Key:JPGQOUSTVILISH-UHFFFAOYSA-N Y
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Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but is no longer in common use.

Enflurane is a structural isomer of isoflurane. It vaporizes readily, but is a liquid at room temperature.

Physical properties

Property	Value
Boiling point at 1 atm	56.5 °C
MAC	1.68
Vapor pressure at 20 °C	22.9 kPa (172 mm Hg)
Blood:gas partition coefficient	1.9
Oil:gas partition coefficient	98

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. Enflurane acts as a positive allosteric modulator of the GABA_A, glycine, and 5-HT₃ receptors, and as a negative allosteric modulator of the AMPA, kainate, and NMDA receptors, as well as of nicotinic acetylcholine receptors.

Side effects

Clinically, enflurane produces a dose-related depression of myocardial contractility with an associated decrease in myocardial oxygen consumption. Between 2% and 5% of the inhaled dose is oxidised in the liver, producing fluoride ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer isoflurane.

Enflurane also lowers the threshold for seizures, and should especially not be used on people with epilepsy. Like all potent inhalation anaesthetic agents it is a known trigger of malignant hyperthermia.

Like the other potent inhalation agents it relaxes the uterus in pregnant women which is associated with more blood loss at delivery or other procedures on the gravid uterus.

The obsolete (as an anaesthetic) agent methoxyflurane had a nephrotoxic effect and caused acute kidney injury, usually attributed to the liberation of fluoride ions from its metabolism. Enflurane is similarly metabolised but the liberation of fluoride results in a lower plasma level and enflurane related kidney failure seemed unusual if seen at all.

Occupational safety

The U.S. National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) for exposure to waste anaesthetic gas of 2 ppm (15.1 mg/m³) over a 60-minute period. Symptoms of occupational exposure to enflurane include eye irritation, central nervous system depression, analgesia, anesthesia, convulsions, and respiratory depression.