ENFLURANE

Details

Stereochemistry	RACEMIC
Molecular Formula	C3H2ClF5O
Molecular Weight	184.492
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)OC(F)(F)C(F)Cl

InChI

InChIKey=JPGQOUSTVILISH-UHFFFAOYSA-N

InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H

HIDE SMILES / InChI

Molecular Formula	C3H2ClF5O
Molecular Weight	184.492
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017087s048lbl.pdf

Enflurane (2-chloro-1,1,2,-trifluoroethyl-difluoromethyl ether) is a halogenated ether structural isomer of isoflurane. 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. 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 oxidized in the liver, producing fluoride ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer isoflurane. The exact mechanism of the action of general anesthetics has not been delineated. Enflurane acts as a positive allosteric modulator of the GABAA, 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glycine receptor 13 Target ID: CHEMBL3392921 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16973644	Positive Allosteric Modulator 179
Glutamate receptor ionotropic AMPA 42 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 42
Glutamate [NMDA] receptor 124 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 42
Glutamate receptor ionotropic kainate 25 Target ID: CHEMBL2109241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 42
GABA-A receptor; anion channel 202 Target ID: CHEMBL2094107 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16973644	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 608 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017087s048lbl.pdf	Primary		Approved 8360	ETHRANE Approved Use INDICATIONS AND USAGE. ĒTHRANE (enflurane, USP) may be used for induction and maintenance of general anesthesia. Enflurane may be used to provide analgesia for vaginal delivery. Low concentrations of enflurane (see DOSAGE AND ADMINISTRATION) may also be used to supplement other general anesthetic agents during delivery by Cesarean section. Higher concentrations of enflurane may produce uterine relaxation and an increase in uterine bleeding. Launch Date 8.3808002E10

C_max

Value	Dose	Co-administered	Analyte	Population
15 μg/mL REVIEW https://www.springer.com/gp/book/9783540117193	2 % single, respiratory dose: 2 % route of administration: Respiratory experiment type: SINGLE co-administered:		ENFLURANE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
60 min REVIEW https://www.springer.com/gp/book/9783540117193	2 % single, respiratory dose: 2 % route of administration: Respiratory experiment type: SINGLE co-administered:		ENFLURANE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 % single, respiratory Dose: 4 % Route: respiratory Route: single Dose: 4 % Sources: https://pubmed.ncbi.nlm.nih.gov/1200833	unhealthy, 25 years n = 1 Health Status: unhealthy Condition: cholecystitis Age Group: 25 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1200833	Disc. AE: Malignant hyperthermia... AEs leading to discontinuation/dose reduction: Malignant hyperthermia Sources: https://pubmed.ncbi.nlm.nih.gov/1200833

AEs

AE	Significance	Dose	Population
Malignant hyperthermia	Disc. AE	4 % single, respiratory Dose: 4 % Route: respiratory Route: single Dose: 4 % Sources: https://pubmed.ncbi.nlm.nih.gov/1200833	unhealthy, 25 years n = 1 Health Status: unhealthy Condition: cholecystitis Age Group: 25 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1200833

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 648

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8162670/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4792	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4792
ChemicalBook	CB1361418	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1361418
MolPort	MolPort-001-773-112	https://www.molport.com/shop/molecule-link/MolPort-001-773-112
eMolecules	890951	https://www.emolecules.com/cgi-bin/more?vid=890951

PubMed

Title	Date	PubMed
The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations.	2000 Feb	10683198
Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.	2000 Jun	10825391
Differential effects of general anesthetics on G protein-coupled inwardly rectifying and other potassium channels.	2001 Jul	11465552
Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: investigation in isolated systemic resistance arteries.	2001 May	11388536
[Biological monitoring of occupational exposure to sevoflurane].	2001 May-Jun	11515150
Myristate, a 14-carbon fatty acid, effectively reverses anesthesia.	2002 Aug	12151949
Fresh gas flow is not the only determinant of volatile agent consumption: a multi-centre study of low-flow anaesthesia.	2002 Jan	11881883
Pre- and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons.	2002 Jul	12086976
The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: a quantitative review.	2002 Jul	12059820
[Calibration of a room air gas monitor with certified reference gases].	2003 Dec	14691626
Fluoride metabolism in smokers and non-smokers following enflurane anaesthesia.	2003 Dec	14633748
The pharmacokinetics of the interstitial space in humans.	2003 Jul 30	12890292
[Effects of enflurane on myocardial reperfusion injury during cardiac surgery with cardiopulmonary bypass].	2003 Jun	12881869
Halogenated inhalational anaesthetics.	2003 Mar	12751547
Carbon monoxide production from sevoflurane breakdown: modeling of exposures under clinical conditions.	2003 Mar	12598259
Evaluation of the mass spectrometric patterns of volatile liquid anaesthetics to predict the temperature--metal caused decomposition pathway.	2003 Mar 17	12628774
An isothermal titration calorimetry study on the binding of four volatile general anesthetics to the hydrophobic core of a four-alpha-helix bundle protein.	2003 Nov	14581228
Mutational analysis of molecular requirements for the actions of general anaesthetics at the gamma-aminobutyric acidA receptor subtype, alpha1beta2gamma2.	2003 Nov 12	14613517
Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function.	2003 Oct 21	14559353
Volatile anaesthetics induce biochemical alterations in the heme pathway in a B-lymphocyte cell line established from hepatoerythropoietic porphyria patients (LBHEP) and in mice inoculated with LBHEP cells.	2004 Feb	14643887

Patents

Sample Use Guides

In Vivo Use Guide

Surgical levels of anesthesia may be maintained with 0.5 to 3.0% enflurane. Maintenance concentrations should not exceed 3.0%. If added relaxation is required, supplemental doses of muscle relaxants may be used. Ventilation to maintain the tension of carbon dioxide in arterial blood in the 35 to 45 mm Hg range is preferred. Hyperventilation should be avoided in order to minimize possible CNS excitation.

Route of Administration: Respiratory

In Vitro Use Guide

Effects of enflurane on NMDA, AMPA, and kainate-gated currents were examined in Xenopus laevis oocytes expressing mouse or human brain mRNA. Enflurane effects on the NMDA, kainate, or AMPA currents were obtained by a preincubation of enflurane alone for 60 s before a coapplication of various drugs and enflurane. Enflurane, at a clinically relevant concentration (1.8 mM), significantly inhibited both maximal and least measurable NMDA, kainate, and AMPA receptor-gated currents.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 00:49:10 UTC 2023` Edited by `admin` on `Thu Jul 06 00:49:10 UTC 2023`
Record UNII	91I69L5AY5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENFLURANE

Official Name

English

ENFLURANE [ORANGE BOOK]

Common Name

English

NSC-115944

Code

English

COMPOUND 347

Common Name

English

enflurane [INN]

Common Name

English

ENFLURANE [VANDF]

Common Name

English

ENFLURANE [MI]

Common Name

English

ETHER, 2-CHLORO-1,1,2-TRIFLUOROETHYL DIFLUOROMETHYL

Systematic Name

English

ANESTHETIC COMPOUND NO. 347

Code

English

ENFLURANE [MART.]

Common Name

English

ENFLURANE [USP IMPURITY]

Common Name

English

ETHRANE

Brand Name

English

ENFLURANE [USP-RS]

Common Name

English

(±)-2-CHLORO-1,1,2-TRIFLUOROETHYL DIFLUOROMETHYL ETHER

Systematic Name

English

ETHANE, 2-CHLORO-1-(DIFLUOROMETHOXY)-1,1,2-TRIFLUORO-

Systematic Name

English

ENFLURANE [GREEN BOOK]

Common Name

English

OHIO 347

Common Name

English

ENFLURANE [USAN]

Common Name

English

ALYRANE

Brand Name

English

Enflurane [WHO-DD]

Common Name

English

347

Code

English

ENFLURANE [JAN]

Common Name

English

ETHANE, 2-CHLORO-1-(DIFLUOROMETHOXY)-1,1,2-TRIFLUORO-, (±)-

Systematic Name

English

R-E-235CA2

Code

English

EFRANE

Brand Name

English

ENFLURANE [USP MONOGRAPH]

Common Name

English

METHYLFLURETHER

Common Name

English

2-CHLORO-1-(DIFLUOROMETHOXY)-1,1,2-TRIFLUOROETHANE

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175975