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Methoxyflurane
Also known as: 76-38-0, Methoxyfluran, Penthrane, Methoflurane, Anecotan, 2,2-dichloro-1,1-difluoroethyl methyl ether
Molecular Formula
C3H4Cl2F2O
Molecular Weight
164.96  g/mol
InChI Key
RFKMCNOHBTXSMU-UHFFFAOYSA-N
FDA UNII
30905R8O7B

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)
1 2D Structure

Methoxyflurane

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2,2-dichloro-1,1-difluoro-1-methoxyethane
2.1.2 InChI
InChI=1S/C3H4Cl2F2O/c1-8-3(6,7)2(4)5/h2H,1H3
2.1.3 InChI Key
RFKMCNOHBTXSMU-UHFFFAOYSA-N
2.1.4 Canonical SMILES
COC(C(Cl)Cl)(F)F
2.2 Other Identifiers
2.2.1 UNII
30905R8O7B
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Anecotan

2. Methofluranum

3. Penthrane

4. Pentrane

2.3.2 Depositor-Supplied Synonyms

1. 76-38-0

2. Methoxyfluran

3. Penthrane

4. Methoflurane

5. Anecotan

6. 2,2-dichloro-1,1-difluoroethyl Methyl Ether

7. Metoxifluran

8. Analgizer

9. Metoxfluran

10. Inhalan

11. 2,2-dichloro-1,1-difluoro-1-methoxyethane

12. Methoxane

13. Metofane

14. Pentrane

15. Methofane

16. Pentran

17. Methoxiflurane

18. Methoxifluranum

19. Ingalan

20. Methoxyfluoran

21. Metossiflurano [dcit]

22. Methoxyfluranum

23. Metoxiflurano

24. Ethane, 2,2-dichloro-1,1-difluoro-1-methoxy-

25. Methoxyfluranum [inn-latin]

26. Metoxiflurano [inn-spanish]

27. Nsc-110432

28. Methyl 1,1-difluoro-2,2-dichloroethyl Ether

29. Penthrox

30. (2,2-dichloro-1,1-difluoroethyl) Methyl Ether

31. Ether, 2,2-dichloro-1,1-difluoroethyl Methyl

32. Da-759

33. Chebi:6843

34. 2,2-dichloro-1,1-difluoroethylmethylether

35. 30905r8o7b

36. Penthrane (van)

37. Metofane (van)

38. Ncgc00168747-01

39. Metossiflurano

40. Penthrane (tn)

41. Ccris 5840

42. Hsdb 7201

43. Einecs 200-956-0

44. Methoxyflurane (usp/inn)

45. Methoxyflurane [anaesthetics, Volatile]

46. Brn 1737766

47. Methoxy Flurane

48. Unii-30905r8o7b

49. Methoxyflurane [usan:usp:inn:ban]

50. Wln: Gygxffo1

51. Dsstox_cid_5556

52. Methoxyflurane [mi]

53. Chembl1341

54. Dsstox_rid_77827

55. Methoxyflurane [inn]

56. Dsstox_gsid_25556

57. Methoxyflurane [hsdb]

58. Methoxyflurane [usan]

59. Methoxy Flurane [jan]

60. Methoxyflurane [vandf]

61. Schembl121229

62. 2,1-difluoro-1-methoxyethane

63. Methoxyflurane [mart.]

64. 2,1-difluoroethyl Methyl Ether

65. Gtpl7234

66. Methoxyflurane [usp-rs]

67. Methoxyflurane [who-dd]

68. Dtxsid7025556

69. Zinc896988

70. Methoxyflurane [green Book]

71. Hy-b0718

72. Tox21_112626

73. Mfcd00040144

74. Nsc110432

75. Methoxyflurane [usp Monograph]

76. Akos006228995

77. Db01028

78. Ks-5167

79. Cas-76-38-0

80. Ether,2-dichloro-1,1-difluoroethyl Methyl

81. Db-019611

82. Cs-0009624

83. Ethane,2-dichloro-1,1-difluoro-1-methoxy-

84. Benzenepropanoic Acid, 4-methoxy-.alpha.-oxo-

85. C07517

86. D00544

87. Q411594

88. Sr-01000944693

89. Sr-01000944693-1

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 164.96 g/mol
Molecular Formula C3H4Cl2F2O
XLogP32.2
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count3
Rotatable Bond Count2
Exact Mass163.9607265 g/mol
Monoisotopic Mass163.9607265 g/mol
Topological Polar Surface Area9.2 Ų
Heavy Atom Count8
Formal Charge0
Complexity75.7
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Anesthetic (inhalation).

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1073


(VET): Anesthetic.

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1073


... Methoxyflurane /is/ indicated for the induction and maintenance of general anesthesia . However, inhalation anesthetic agents are rarely used alone; other medications are frequently administered to induce or supplement anesthesia. /Included in US product labeling/

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


... Methoxyflurane ... /is/ indicated in low doses to provide analgesia for procedures not requiring loss of consciousness. /Included in US product labeling/

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


For more Therapeutic Uses (Complete) data for METHOXYFLURANE (6 total), please visit the HSDB record page.


4.2 Drug Warning

Inhalation anesthetics cross the placenta. Risk-benefit must be considered because studies (by retrospective survey) of operating room personnel chronically exposed to low concentrations of inhalation anesthetics indicate that pregnancies in female personnel and wives of male personnel may be subject to an increased incidence of spontaneous abortions, stillbirths, and possibly birth defects . However, the methods used in obtaining and interpreting the data in these studies have been questioned. /Inhalation anesthetics/

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


Because of potential nephrotoxicity, administration of methoxyflurane in concentrations sufficient to produce muscle relaxation is not recommended ; a neuromuscular blocking agent should be used concurrently if necessary. Also, it is recommended that methoxyflurane not be used during vascular surgery at or near renal blood vessels.

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


Caution needed in diabetes, uncontrolled or with polyuria or obesity; in renal function impairment of disease; or in toxemia of pregnancy, as methoxyflurane may increase the risk of nephrotoxicity.

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


Monitoring of renal function may be needed to detect possible nephrotoxicity if patient's postoperative urine output is excessive.

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


Methoxyflurane, a general anesthetic, is a known nephrotoxin. A case is presented that demonstrated diffuse, bilateral renal cortical calcification on CT secondary to repeated methoxyflurane inhalation.

PMID:3335658 Brennan RP et al; J Comput Assist Tomogr 12 (1): 155-6 (1988)


4.3 Drug Indication

For use in the induction and maintenance of general anesthesia


Treatment of acute pain


5 Pharmacology and Biochemistry
5.1 Pharmacology

Methoxyflurane 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.


5.2 MeSH Pharmacological Classification

Anesthetics, Inhalation

Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173) (See all compounds classified as Anesthetics, Inhalation.)


5.3 ATC Code

N - Nervous system

N02 - Analgesics

N02B - Other analgesics and antipyretics

N02BG - Other analgesics and antipyretics

N02BG09 - Methoxyflurane


5.4 Absorption, Distribution and Excretion

Elimination: Primary: 35% excreted unchanged by exhalation.

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


Inhalation anesthetics are rapidly absorbed into the circulation via the lungs. /Inhalation anesthetics/

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


The urinary fluoride ion concentration was compared in 2 series of parturients, the one receiving methoxyflurane-nitrous oxide analgesia during labor and the other nitrous oxide analgesia. Results showed that in the methoxyflurane-nitrous oxide analgesia series, both the mothers and the neonates showed a significantly higher urinary fluoride ion concentration in comparison to the nitrous analgesia series. The urinary fluoride concentration was related to the vaporized amount of methoxyflurane.

PMID:716954 Dahlgren BE; Acta Pharm Suec 15 (3): 211-7 (1978)


5.5 Metabolism/Metabolites

Hepatic.


Biotransformation - 50% of dose metabolized. A substantial quantity of inorganic fluoride is formed; also metabolized to other potentially nephrotoxic substances.

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


5.6 Mechanism of Action

Methoxyflurane 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.


Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. The mechanisms of fluoride toxicity on an immortalized cell line /was investigated/. Cells were cultured for 2, 6 or 24 hr in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. ... At 5 mmol after 24 hr, fluoride decreased cell numbers (-14%, *P < 0.05), protein content (-16%*), leucine incorporation (-54%*), Na-K-2Cl activity (-84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24hr and after 2 hr at 5 mmol. Crystal formation in mitochondria occurred after 6 hr at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride. The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.

PMID:12095014 Cittanove ML et al; Eur J Anaesthesiol 19 (5): 341-9 (2002)


The precise mechanism by which inhalation anesthetics produce loss of perception of sensations and unconsciousness is not known. Inhaled anesthetics act at many areas in the CNS. The Meyer-Overton theory suggests that the site of action of inhalation anesthetics may be the lipid matrix of neuronal membranes or other lipophilic sites. Anesthetics may cause changes in membrane thickness, which in turn affect the gating properties of ion channels in neurons. Interference with the hydrophobic portion of neuronal ion channel membrane proteins may be an important mechanism. /Inhalation anesthetics/

Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004.


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