METHOXYFLURANE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C3H4Cl2F2O
Molecular Weight	164.966
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(F)(F)C(Cl)Cl

InChI

InChIKey=RFKMCNOHBTXSMU-UHFFFAOYSA-N

InChI=1S/C3H4Cl2F2O/c1-8-3(6,7)2(4)5/h2H,1H3

HIDE SMILES / InChI

Molecular Formula	C3H4Cl2F2O
Molecular Weight	164.966
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB01028
Curator's Comment: description was created based on several sources, including https://www.fda.gov/ohrms/dockets/98fr/04p-0379-nwl0001.pdf

Methoxyflurane is an inhalation anesthetic. Methoxyflurane was used for surgical, obstetric, or dental anesthesia, but was withdrawn from US market due to safety concerns, but is still in use in Australia and other countries. Methoxyflurane induces muscle relaxation and reduces pains sensitivity by altering tissue excitability by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
synaptic transmission 2 Target ID: GO:0007268 Sources: https://www.ncbi.nlm.nih.gov/pubmed/550880	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: http://www.medsafe.govt.nz/profs/Datasheet/p/penthroxinh.pdf	Primary		Approved 8429	PENTHROX Approved Use For emergency relief of pain by self administration in conscious haemodynamically stable patients with trauma and associated pain, under supervision of personnel trained in its use. For the relief of pain in monitored conscious patients who require analgesia for surgical procedures such as the change of dressings.

T_1/2

Value	Dose	Co-administered	Analyte	Population
5 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3706798/	0.047 % other, respiratory dose: 0.047 % route of administration: Respiratory experiment type: OTHER co-administered:		METHOXYFLURANE unknown	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mL 1 times / day multiple, respiratory Highest studied dose Dose: 60 mL, 1 times / day Route: respiratory Route: multiple Dose: 60 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32593381 https://pubmed.ncbi.nlm.nih.gov/3452163/	unhealthy n = 2 Health Status: unhealthy Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/32593381 https://pubmed.ncbi.nlm.nih.gov/3452163/	Other AEs: Renal failure... Other AEs: Renal failure (grade 5, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/32593381 https://pubmed.ncbi.nlm.nih.gov/3452163/
2 mL 2 times / day multiple, respiratory Dose: 2 mL, 2 times / day Route: respiratory Route: multiple Dose: 2 mL, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3971205	unhealthy n = 1 Health Status: unhealthy Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3971205	Disc. AE: Hepatitis... AEs leading to discontinuation/dose reduction: Hepatitis Sources: https://pubmed.ncbi.nlm.nih.gov/3971205

AEs

AE	Significance	Dose	Population
Renal failure	grade 5, 2 patients	60 mL 1 times / day multiple, respiratory Highest studied dose Dose: 60 mL, 1 times / day Route: respiratory Route: multiple Dose: 60 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32593381 https://pubmed.ncbi.nlm.nih.gov/3452163/	unhealthy n = 2 Health Status: unhealthy Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/32593381 https://pubmed.ncbi.nlm.nih.gov/3452163/
Hepatitis	Disc. AE	2 mL 2 times / day multiple, respiratory Dose: 2 mL, 2 times / day Route: respiratory Route: multiple Dose: 2 mL, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3971205	unhealthy n = 1 Health Status: unhealthy Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3971205

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 667 CYP1A2 1054 CYP2A6 543 CYP2B6 664

Drug as victim

Target	Modality	Activity
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8214760/	major
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8214760/	minor
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8214760/	minor
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/7879937/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/7879937/	yes
CYP3A4 1737	substrate 3367 Sources: DOI: 10.1097/00000542-199503000-00011	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6843	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6843
ChemicalBook	CB6314297	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6314297
MolPort	MolPort-000-153-984	https://www.molport.com/shop/molecule-link/MolPort-000-153-984
ZINC	ZINC000000896988	http://zinc15.docking.org/substances/ZINC000000896988
eMolecules	891340	https://www.emolecules.com/cgi-bin/more?vid=891340

PubMed

Title	Date	PubMed
Renal and hepatic injury associated with methoxyflurane anesthesia.	1968 Dec	5725736
Nephropathy associated with methoxyflurane anesthesia. A follow-up report.	1968 Sep 9	5695293
The effect of methoxyflurane on cerebrospinal fluid pressure in patients with and without intracranial space-occupying lesions.	1969 Jul	5798834
[Halogenated hydrocarbon compounds in anesthesia and their effect on the liver. Liver necrosis and tubulus degeneration after repeated methoxyflurane anesthesia].	1971	5140659
Recurrent hepatitis due to methoxyflurane anesthesia.	1971 Apr 29	5551804
Irreversible acute oliguric renal failure. A complication of methoxyflurane anesthesia.	1972 Apr 20	5061073
Renal failure after methoxyflurane anaesthesia.	1972 Jan	5007641
Repeated methoxyflurane analgesia for burns dressings.	1972 Jun	5045566
Anesthetic malignant myopathy hyperthermia.	1972 Sep	5081936
Methoxyflurane (penthrane) inhalation in labor.	1973 Jun	4541086
Interstitial fibrosis and chronic renal failure following methoxyflurane anesthesia.	1973 Mar 12	4739327
Letter: Partial recovery from renal failure following methoxyflurane anesthesia.	1974 Jan 14	4859609
The syndrome of methoxyflurane-associated hepatitis.	1974 Mar	4816183
Letter: Nonoliguric renal failure and enflurane.	1974 Oct	4414316
Flecked retina. Appearance secondary to oxalate crystals from methoxyflurane anesthesia.	1975 Jan	1111483
Influence of phenobarbital pretreatment on methoxyflurane and sodium fluoride nephropathy in Fischer 344 Rats.	1976 Aug	982456
Toxic nephropathy after low-dose methoxyflurane anesthesia: drug interaction with secobarbital?	1976 Feb 21	1253070
Methoxyflurane hepatitis.	1977 Nov	918705
Hepatic and renal effects of low concentrations of methoxyflurane in exposed delivery ward personnel.	1980 Dec	7218059
Methoxyflurane hepatitis: two cases following obstetric analgesia.	1983 Feb	6133801
[Massive oxalosis of the kidney in association with anesthesia using methoxyflurane].	1984 Aug	6499021
Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity.	1995 Mar	7879937
In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells.	2003 Jul 21	12865937
A replacement for methoxyflurane (Metofane) in open-circuit anaesthesia.	2004 Jul	15207039
Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice.	2005 Dec 5	16324223
Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: an experimental murine model.	2005 May 25	15916706
New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway.	2006 Oct	17006072
Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes.	2007 Jun 27	17597533
A review of patients who suddenly deteriorate in the presence of paramedics.	2008 Jul 26	18655721
Changes in biologic and/or immunologic parameters induced by intratracheal instillation of pregnant mice with benzo(a)pyrene are potentially confounded by anesthesia.	2010 Jun	20384551

Patents

Sample Use Guides

In Vivo Use Guide

One bottle of PENTHROX® (1.5 mL or 3 mL) to be vaporised in a PENTHROX inhaler. On finishing the initial bottle, another bottle may be used. Up to 6 mL may be administered per day. The refilling must be conducted in a well ventilated area to reduce environmental exposure to Methoxyflurane vapour.

Route of Administration: Respiratory

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:03:05 UTC 2023` Edited by `admin` on `Fri Dec 15 15:03:05 UTC 2023`
Record UNII	30905R8O7B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHOXYFLURANE

Official Name

English

METHOXIFLURANE

Common Name

English

METHOXYFLURANE [USP MONOGRAPH]

Common Name

English

2,2-Dichloro-1,1-difluoroethyl methyl ether

Systematic Name

English

PENTHRANE

Brand Name

English

METHOXYFLURANE [HSDB]

Common Name

English

Methoxyflurane [WHO-DD]

Common Name

English

METHYL 1,1-DIFLUORO-2,2-DICHLOROETHYL ETHER

Systematic Name

English

ETHANE, 2,2-DICHLORO-1,1-DIFLUORO-1-METHOXY-

Systematic Name

English

INHALAN

Common Name

English

METHOXYFLURANE [USAN]

Common Name

English

METHOXYFLURANE [USP-RS]

Common Name

English

ANALGIZER

Common Name

English

METHOXY FLURANE [JAN]

Common Name

English

PENTHROX

Brand Name

English

methoxyflurane [INN]

Common Name

English

ANECOTAN

Common Name

English

METHOXYFLURANE [MART.]

Common Name

English

METHOXYFLURANE [GREEN BOOK]

Common Name

English

METHOXYFLURANE [MI]

Common Name

English

NSC-110432

Code

English

METHOXYFLURANE [VANDF]

Common Name

English

DA-759

Code

English

Classification Tree Code System Code

WHO-ATC

N02BG09