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

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 Methoxyflurane was used for surgical, obstetric, or dental anesthesia, but was withdrawn from US market due to safety concerns, but is still in use in Australia and other countries.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
Nephropathy associated with methoxyflurane anesthesia. A follow-up report.	1968 Sep 9	5695293
Hazards of methoxyflurane emulsions in man.	1968 Sep-Oct	4876884
Hepatic coma associated with methoxyflurane anesthesia. Report of a case.	1970 Aug	5455938
Halothane anesthesia following methoxyflurane-induced nephrotoxicity.	1970 Oct	5525298
Toxicity following methoxyflurane anesthesia. I. Clinical and pathological observations in two fatal cases.	1970 Oct 5	5469063
Renal oxalosis and azotemia after methoxyflurane anesthesia.	1970 Sep 24	5454752
[Halogenated hydrocarbon compounds in anesthesia and their effect on the liver. Liver necrosis and tubulus degeneration after repeated methoxyflurane anesthesia].	1971	5140659
Methoxyflurane metabolism and renal dysfunction: clinical correlation in man.	1971 Sep	5095537
Methoxyflurane and renal dysfunction.	1971 Sep 27	5109740
[Renal tubular necrosis and cytolytic hepatitis following repeated anaesthetic inhalation of methoxyflurane].	1972 Jul-Aug	4649400
Repeated methoxyflurane analgesia for burns dressings.	1972 Jun	5045566
Combined nephrotoxicity of gentamicin and methoxyflurane anaesthesia in man. A case report.	1973 Apr	4705491
An animal model for combined methoxyflurane and gentamicin nephrotoxicity.	1973 Apr	4705480
Occasional occurrence of serious renal complications after methoxyflurane (Penthrane) anesthesia.	1973 Aug	4722675
Strain differences in metabolism and susceptibility to the nephrotoxic effects of methoxyflurane in rats.	1973 Feb	4688183
Methoxyflurane (penthrane) inhalation in labor.	1973 Jun	4541086
Persisting renal insufficiency after methoxyflurane anesthesia. Report of two cases and review of literature.	1974 Apr	4818422
Letter: Partial recovery from renal failure following methoxyflurane anesthesia.	1974 Jan 14	4859609
The syndrome of methoxyflurane-associated hepatitis.	1974 Mar	4816183
Unilateral nephrotoxicity associated with methoxyflurane anesthesia: a case report.	1974 Mar-Apr	4856134
Incidence of tubular degeneration with microlithiasis following methoxyflurane compared with other anesthetic agents.	1974 May-Jun	4856932
The etiology of methoxyflurane nephrotoxicity.	1974 Sep	4416261
Influence of phenobarbital pretreatment on methoxyflurane and sodium fluoride nephropathy in Fischer 344 Rats.	1976 Aug	982456
[Primary hyperoxaluria. Clinical, histological and crystallographic study of the ocular lesions].	1976 Feb	180940
The effect of enflurane, isoflurane, fluroxene, methoxyflurane and diethyl ether anesthesia on ouabain tolerance in the dog.	1976 May-Jun	5922
Methoxyflurane hepatitis.	1977 Nov	918705
[Adverse effects of modern inhalation anesthetics. 2. Control of amounts and elimination of escaping anesthesia gases].	1978 Dec 14	721016
Anesthetic indices--further data.	1978 Mar	626424
Methoxyflurane-induced nephrotoxicity: influence of food intake on some biochemical indicators of renal function in Fischer 344 rats.	1978 Sep	725934
Hepatic and renal effects of low concentrations of methoxyflurane in exposed delivery ward personnel.	1980 Dec	7218059
Deuterated methoxyflurane anesthesia and renal function in Fischer 344 rats.	1982 Mar	7059030
Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane.	1982 Oct-Dec	6985498
[Massive oxalosis of the kidney in association with anesthesia using methoxyflurane].	1984 Aug	6499021
Hepatic and renal effects of prolonged exposure of rats to 50 p.p.m. methoxyflurane.	1985 Sep	4061098
Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers.	2004 Jan 12	14710236
Neutron analysis of spent fuel storage installation using parallel computing and advance discrete ordinates and Monte Carlo techniques.	2005	16604721
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
Tumor-specific expression of alphavbeta3 integrin promotes spontaneous metastasis of breast cancer to bone.	2006	16608535
Modulation of T cell function by combination of epitope specific and low dose anticytokine therapy controls autoimmune arthritis.	2006 Dec 20	17183718
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
Differential sensitivity to anticholinesterase insecticides in the juvenile rat: effects on thermoregulation.	2007 Mar 1	17454568
Multiple dendritic cell populations activate CD4+ T cells after viral stimulation.	2008 Feb 27	18301768
Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice.	2008 Jul 15	18627612
A review of patients who suddenly deteriorate in the presence of paramedics.	2008 Jul 26	18655721
Isoflavones prevent bone loss following ovariectomy in young adult rats.	2008 Mar 2	18312690
Non-invasive measurements of exhaled NO and CO associated with methacholine responses in mice.	2008 May 27	18505586
Bacterial antigen expression is an important component in inducing an immune response to orally administered Salmonella-delivered DNA vaccines.	2009 Jun 26	19557169
Prevention and treatment of influenza with hyperimmune bovine colostrum antibody.	2010 Oct 26	21049034

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

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