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Identification
NameMethoxyflurane
Accession NumberDB01028  (APRD00744)
Typesmall molecule
Groupsapproved
Description

An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with nitrous oxide to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)

Structure
Thumb
Synonyms
SynonymLanguageCode
MethoxyfluranumLatinINN
MetoxifluranoSpanishINN
SaltsNot Available
Brand names
NameCompany
PenthraneAbbott Laboratories
Brand mixturesNot Available
Categories
CAS number76-38-0
WeightAverage: 164.966
Monoisotopic: 163.960726574
Chemical FormulaC3H4Cl2F2O
InChI KeyRFKMCNOHBTXSMU-UHFFFAOYSA-N
InChI
InChI=1S/C3H4Cl2F2O/c1-8-3(6,7)2(4)5/h2H,1H3
IUPAC Name
2,2-dichloro-1,1-difluoro-1-methoxyethane
SMILES
COC(F)(F)C(Cl)Cl
Mass Specshow(7.12 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsEthers; Organofluorides; Organochlorides; Alkyl Fluorides; Alkyl Chlorides
Substituentsorganofluoride; organochloride; organohalogen; alkyl halide; alkyl fluoride; alkyl chloride
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor use in the induction and maintenance of general anesthesia
PharmacodynamicsMethoxyflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.
Mechanism of actionMethoxyflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Methoxyflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Methoxyflurane also binds to the GABA receptor, the large conductance Ca2+ activated potassium channel, the glutamate receptor and the glycine receptor.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLD50=3600 mg/kg (Orally in rats). Symptoms of overexposure include eye irritation, CNS depression, analgesia, anesthesia, seizures, respiratory depression, and liver and kidney damage.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9921
Caco-2 permeable + 0.6119
P-glycoprotein substrate Non-substrate 0.8535
P-glycoprotein inhibitor I Non-inhibitor 0.9588
P-glycoprotein inhibitor II Non-inhibitor 0.9203
Renal organic cation transporter Non-inhibitor 0.9227
CYP450 2C9 substrate Non-substrate 0.7959
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.6542
CYP450 1A2 substrate Non-inhibitor 0.6508
CYP450 2C9 substrate Non-inhibitor 0.8587
CYP450 2D6 substrate Non-inhibitor 0.9407
CYP450 2C19 substrate Non-inhibitor 0.6081
CYP450 3A4 substrate Non-inhibitor 0.9753
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8956
Ames test Non AMES toxic 0.9132
Carcinogenicity Carcinogens 0.7261
Biodegradation Not ready biodegradable 0.9737
Rat acute toxicity 1.6296 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9515
hERG inhibition (predictor II) Non-inhibitor 0.9016
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point-35 °CPhysProp
boiling point105 °CPhysProp
water solubility2.83E+004 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.21HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility6.46e+00 g/lALOGPS
logP2.01ALOGPS
logP2.31ChemAxon
logS-1.4ALOGPS
pKa (strongest basic)-4.5ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area9.23ChemAxon
rotatable bond count2ChemAxon
refractivity27.97ChemAxon
polarizability11.46ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00544
KEGG CompoundC07517
PubChem Compound4116
PubChem Substance46508879
ChemSpider3973
Therapeutic Targets DatabaseDAP000682
PharmGKBPA450434
Drug Product Database2019027
WikipediaMethoxyflurane
ATC CodesN02BG09
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(52.9 KB)
Interactions
Drug Interactions
Drug
DemeclocyclineThe tetracycline, demeclocycline, may increase the renal toxicity of methoxyflurane.
MinocyclineThe tetracycline, minocycline, may increase the renal toxicity of methoxyflurane.
PhenobarbitalThe barbiturate, phenobarbital, increases the renal toxicity of methoxyflurane.
PrimidoneThe barbiturate, primidone, increases the renal toxicity of methoxyflurane.
TetracyclineTetracycline may increase the renal toxicity of methoxyflurane.
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Moody EJ, Suzdak PD, Paul SM, Skolnick P: Modulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics. J Neurochem. 1988 Nov;51(5):1386-93. Pubmed
  4. Moody EJ, Skolnick P: The imidazobenzodiazepine Ro 15-4513 antagonizes methoxyflurane anesthesia. Life Sci. 1988;43(16):1269-76. Pubmed
  5. Krasowski MD, Harrison NL: The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br J Pharmacol. 2000 Feb;129(4):731-43. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glutamate receptor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor 1 P42261 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Martin DC, Plagenhoef M, Abraham J, Dennison RL, Aronstam RS: Volatile anesthetics and glutamate activation of N-methyl-D-aspartate receptors. Biochem Pharmacol. 1995 Mar 15;49(6):809-17. Pubmed

3. Glycine receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glycine receptor subunit alpha-1 P23415 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Krasowski MD, Harrison NL: The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br J Pharmacol. 2000 Feb;129(4):731-43. Pubmed

4. Calcium-transporting ATPase type 2C member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Calcium-transporting ATPase type 2C member 1 P98194 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lopez MM, Kosk-Kosicka D: How do volatile anesthetics inhibit Ca(2+)-ATPases? J Biol Chem. 1995 Nov 24;270(47):28239-45. Pubmed

5. Potassium voltage-gated channel subfamily A member 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily A member 1 Q09470 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Elliott JR, Elliott AA, Harper AA, Winpenny JP: Effects of general anaesthetics on neuronal sodium and potassium channels. Gen Pharmacol. 1992 Nov;23(6):1005-11. Pubmed

6. ATP synthase subunit delta, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
ATP synthase subunit delta, mitochondrial P30049 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. NADH-ubiquinone oxidoreductase chain 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
NADH-ubiquinone oxidoreductase chain 1 P03886 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. ChEMBL Compound Report Card (Accessed December 2013)

Enzymes

1. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13