ENFLURANE

Details

Stereochemistry	RACEMIC
Molecular Formula	C3H2ClF5O
Molecular Weight	184.4924
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	184.4924
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 155
Glutamate receptor ionotropic AMPA 40 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 37
Glutamate [NMDA] receptor 123 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 37
Glutamate receptor ionotropic kainate 25 Target ID: CHEMBL2109241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7681790	Negative Allosteric Modulator 37
GABA-A receptor; anion channel 189 Target ID: CHEMBL2094107 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16973644	Positive Allosteric Modulator 155

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 580 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017087s048lbl.pdf	Primary		Approved 7997	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 567

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 567	substrate 2752 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 relationship of brain catecholamine levels to enflurane requirements among three strains of mice with different anesthetic sensitivities.	2001	14566529
Myristate, a 14-carbon fatty acid, effectively reverses anesthesia.	2002 Aug	12151949
Effects of halothane and enflurane anesthesia on sympathetic beta-adrenoreceptor-mediated pulmonary vasodilation in chronically instrumented dogs.	2002 Aug	12151940
A second-generation blood substitute (perflubron emulsion) increases the blood solubility of modern volatile anesthetics in vitro.	2002 Aug	12145053
PKQuest: measurement of intestinal absorption and first pass metabolism - application to human ethanol pharmacokinetics.	2002 Aug 15	12182761
PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol.	2002 Aug 15	12182760
An unusual case of driving under the influence of enflurane.	2002 Aug 28	12175964
An assessment of the cerebroprotective potential of volatile anaesthetics using two independent methods in an in vitro model of cerebral ischaemia.	2002 Dec 27	12470875
Combined effect of hypothermia and crystalloid hemodilution on the solubility of volatile anesthetics in human blood.	2002 Jul	12150733
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
The effects of drugs used in anaesthesia on platelet membrane receptors and on platelet function.	2002 Jun	12041738
The minimum local anesthetic concentration of ropivacaine for caudal analgesia in children.	2002 Jun	12032008
Degrees of aversion shown by rats and mice to different concentrations of inhalational anaesthetics.	2002 Jun 29	12120924
Respiratory response to skin incision during anaesthesia with infusions of propofol and alfentanil.	2002 May	12067001
A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs.	2002 May 20	12085211
Experimental investigation of the behavior of gas phase simulated moving beds.	2002 May 31	12113344
Myocardial protection by anesthetic agents against ischemia-reperfusion injury: an update for anesthesiologists.	2002 Oct	12374705
Anesthetic and ethanol effects on spontaneously opening glycine receptor channels.	2002 Sep	12354281
Mice with glycine receptor subunit mutations are both sensitive and resistant to volatile anesthetics.	2002 Sep	12198041
PKQuest: capillary permeability limitation and plasma protein binding - application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics.	2002 Sep 26	12323078
Effect of isolation stress on anesthetic requirement in mice.	2003	12903928
Comparison of the effects of neuroleptanesthesia and enflurane or sevoflurane anesthesia on neuromuscular blockade by rocuronium.	2003	12903925
Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma.	2003 Aug 18	12915890
[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
Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na+ channels, Ca2+ channels, and GABA(A) receptors.	2003 Feb	12538378
General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit.	2003 Feb	12475885
Anaesthetic agents in adult day case surgery.	2003 Jan	12553381
Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by rat alveolar type II cells in primary culture.	2003 Jan	12502982
Enflurane as an internal standard in monitoring halogenated volatile anaesthetics by headspace gas chromatography-mass spectrometry.	2003 Jan 24	12580493
A new method of inhalation anesthesia with nasopharyngeal insufflation in rat experiment.	2003 Jul	14562613
Resuscitation from hemorrhagic shock: experimental model comparing normal saline, dextran, and hypertonic saline solutions.	2003 Jul	12847383
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
The effects of enflurane, isoflurane, and intravenous anesthetics on rat diaphragmatic function and fatigability.	2003 Jun	12760994
Cold and mechanical allodynia in both hindpaws and tail following thoracic spinal cord hemisection in rats: time courses and their correlates.	2003 Jun 12	12770696
Halogenated inhalational anaesthetics.	2003 Mar	12751547
Volatile anesthetics regulate pulmonary vascular tension through different potassium channel subtypes in isolated rabbit lungs.	2003 Mar	12620956
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
[Drug-induced seizures].	2003 Mar 31	12715674
Interaction between artificial membranes and enflurane, a general volatile anesthetic: DPPC-enflurane interaction.	2003 May	12719242
Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions.	2003 May	12707133
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
Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis.	2003 Oct 6	14520469
The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits.	2003 Sep	12960553
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 `Fri Jun 25 20:55:03 UTC 2021` Edited by `admin` on `Fri Jun 25 20:55:03 UTC 2021`
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

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 [USP]

Common Name

English

ENFLURANE [GREEN BOOK]

Common Name

English

OHIO 347

Common Name

English

ENFLURANE [USAN]

Common Name

English

ALYRANE

Brand Name

English

347

Code

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