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2D Structure
Also known as: 54-36-4, 2-methyl-1,2-di-3-pyridyl-1-propanone, Metopirone, Methopyrapone, Metopiron, Methapyrapone
Molecular Formula
C14H14N2O
Molecular Weight
226.27  g/mol
InChI Key
FJLBFSROUSIWMA-UHFFFAOYSA-N
FDA UNII
ZS9KD92H6V

An inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.
Metyrapone is an Adrenal Steroid Synthesis Inhibitor. The mechanism of action of metyrapone is as an Adrenal Steroid Synthesis Inhibitor.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-methyl-1,2-dipyridin-3-ylpropan-1-one
2.1.2 InChI
InChI=1S/C14H14N2O/c1-14(2,12-6-4-8-16-10-12)13(17)11-5-3-7-15-9-11/h3-10H,1-2H3
2.1.3 InChI Key
FJLBFSROUSIWMA-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC(C)(C1=CN=CC=C1)C(=O)C2=CN=CC=C2
2.2 Other Identifiers
2.2.1 UNII
ZS9KD92H6V
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Mtopirone

2. Methbipyranone

3. Methopyrapone

4. Metopiron

5. Metopirone

6. Su 4885

2.3.2 Depositor-Supplied Synonyms

1. 54-36-4

2. 2-methyl-1,2-di-3-pyridyl-1-propanone

3. Metopirone

4. Methopyrapone

5. Metopiron

6. Methapyrapone

7. Methopirapone

8. Methopyrinine

9. Methopyrone

10. Metopyrone

11. Metyrapon

12. Methbipyranone

13. Mepyrapone

14. Metroprione

15. Metapirone

16. Metapyron

17. Metirapona

18. Metyraponum

19. 2-methyl-1,2-dipyridin-3-ylpropan-1-one

20. Su 4885

21. 1-propanone, 2-methyl-1,2-di-3-pyridinyl-

22. 2-methyl-1,2-di(pyridin-3-yl)propan-1-one

23. 2-methyl-1,2-di-3-pyridinyl-1-propanone

24. 2-methyl-1,2-bis(3-pyridyl)-1-propanone

25. Nsc 25265

26. Nsc-25265

27. 1-propanone, 2-methyl-1,2-di-3-pyridyl-

28. Chembl934

29. Zs9kd92h6v

30. Chebi:44241

31. 2-methyl-1,2-bis(pyridin-3-yl)propan-1-one

32. Cas-54-36-4

33. Ncgc00016242-01

34. Dsstox_cid_3314

35. Dsstox_rid_76971

36. Dsstox_gsid_23314

37. Metyraponum [inn-latin]

38. Metirapona [inn-spanish]

39. Myt

40. Smr000059134

41. 1,2-di-3-pyridyl-2-methyl-1-propanone

42. Hsdb 2500

43. Metopirone (tn)

44. Einecs 200-206-2

45. Unii-zs9kd92h6v

46. 1-propanone, 1,2-di-3-pyridyl-2-methyl-

47. Metyrapone [usan:usp:inn:ban:jan]

48. Metyrapone [mi]

49. Metyrapone [inn]

50. Metyrapone [jan]

51. 2-methyl-1,2-bis(3-pyridyl)propan-1-one

52. Prestwick0_000904

53. Prestwick1_000904

54. Prestwick2_000904

55. Prestwick3_000904

56. Metyrapone [hsdb]

57. Metyrapone [usan]

58. 2-methyl-1,2-dipyridin-3-yl-propan-1-one

59. Metyrapone [vandf]

60. Metyrapone [mart.]

61. Metyrapone [usp-rs]

62. Metyrapone [who-dd]

63. Bidd:pxr0082

64. Bspbio_000748

65. Mls001066377

66. Mls001335881

67. Mls001335882

68. Schembl637432

69. Spbio_002947

70. 1-propanone,2-di-3-pyridyl-

71. Amy832

72. Bpbio1_000824

73. Gtpl5224

74. Metyrapone (jp17/usp/inn)

75. Zinc1728

76. Dtxsid1023314

77. Metyrapone [orange Book]

78. 1-propanone,2-di-3-pyridinyl-

79. Hms1570f10

80. Hms2094i07

81. Hms2097f10

82. Hms2235e16

83. Hms3259o05

84. Hms3371b16

85. Hms3714f10

86. Hms3742e21

87. Hms3869k13

88. Metyrapone [usp Monograph]

89. Pharmakon1600-01506014

90. Bcp19099

91. Ex-a1403

92. Hy-b1232

93. Nsc25265

94. Tox21_110323

95. Bdbm50028166

96. Nsc760076

97. S5416

98. Akos015919707

99. Metyrapone, >=98% (hplc), Solid

100. Tox21_110323_1

101. Ccg-213598

102. Cs-4879

103. Db01011

104. Nc00462

105. Nsc-760076

106. Ncgc00016242-02

107. Ncgc00016242-03

108. Ncgc00016242-05

109. Ncgc00161837-01

110. As-56195

111. Db-052546

112. Ab00513955

113. B7347

114. Eu-0009322

115. Ft-0603230

116. Su-4885; Su 4885; Su4885

117. 2-methyl-1,2-di(3-pyridinyl)-1-propanone #

118. C07205

119. D00410

120. D70339

121. 2-methyl-1,2-di-3-pyridyl-1-propanone, 96%

122. Ab00513955_07

123. 054m364

124. A830124

125. Q821641

126. Sr-01000765398

127. Sr-01000765398-2

128. Brd-k46862739-001-03-6

129. Metyrapone, United States Pharmacopeia (usp) Reference Standard

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 226.27 g/mol
Molecular Formula C14H14N2O
XLogP32
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count3
Rotatable Bond Count3
Exact Mass226.110613074 g/mol
Monoisotopic Mass226.110613074 g/mol
Topological Polar Surface Area42.8 Ų
Heavy Atom Count17
Formal Charge0
Complexity275
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 Drug Information
1 of 2  
Drug NameMetopirone
PubMed HealthMetyrapone (By mouth)
Drug ClassesDiagnostic Agent, Pituitary Function
Drug LabelMetopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteriod synthesis, available as 250-mg capsules for oral administration. Its chemical name is 2-methyl-1, 2-di-3-pyridyl-1-propanone, and its structural formula isMetopirone s...
Active IngredientMetyrapone
Dosage FormCapsule
RouteOral
Strength250mg
Market StatusPrescription
CompanyHra Pharma

2 of 2  
Drug NameMetopirone
PubMed HealthMetyrapone (By mouth)
Drug ClassesDiagnostic Agent, Pituitary Function
Drug LabelMetopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteriod synthesis, available as 250-mg capsules for oral administration. Its chemical name is 2-methyl-1, 2-di-3-pyridyl-1-propanone, and its structural formula isMetopirone s...
Active IngredientMetyrapone
Dosage FormCapsule
RouteOral
Strength250mg
Market StatusPrescription
CompanyHra Pharma

4.2 Therapeutic Uses

METYRAPONE IS USED TO TEST ABILITY OF PITUITARY TO RESPOND TO DECR CONCN OF PLASMA CORTISOL. ADMIN...TO PT WITH DISEASE OF HYPOTHALAMICO-PITUITARY COMPLEX.../IS/ NOT FOLLOWED BY INCR RENAL EXCRETION OF "17-HYDROXYCORTICOIDS."

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


.../METYRAPONE HAS/ BEEN USED WITH SPIRONOLACTONE & PREDNISONE TO RELIEVE SEVERE EDEMA, BUT...HAS BEEN REPLACED BY MORE POTENT DIURETICS. .../ALSO/ USED INVESTIGATIONALLY TO LOWER PLASMA CHOLESTEROL LEVELS IN PT WITH FAMILIAL HYPERCHOLESTEROLEMIA TYPE II, BUT WELL-CONTROLLED CLINICAL STUDIES...NOT YET AVAILABLE.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


METYRAPONE MAY BE USED TO CONFIRM DEXAMETHASONE SUPPRESSION TEST RESULTS IN DIFFERENTIAL DIAGNOSIS OF ADRENAL HYPERPLASIA & ADRENAL ADENOMA...RESULTS OF THIS TEST MUST BE INTERPRETED CAUTIOUSLY.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


METYRAPONE HAS BEEN USED EXPTL TO TREAT HYPERCORTISOLISM THAT RESULTS FROM ADRENAL NEOPLASMS THAT FUNCTION AUTONOMOUSLY & FROM ECTOPIC ACTH PRODUCTION BY TUMORS. IT IS NOT SUITABLE FOR CORRECTING EXCESSIVE CORTISOL SECRETION OF CUSHING'S SYNDROME CAUSED BY HYPERSECRETION OF PITUITARY ACTH.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


...ADMIN OF METYRAPONE CAN BE USED AS TEST FOR NORMAL HYPOTHALAMICO-PITUITARY FUNCTION ONLY IF ADRENAL GLANDS ARE CAPABLE OF RESPONDING TO ACTH...

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


4.3 Drug Warning

IN HIGH DOSES, METYRAPONE MAY INHIBIT 18- & 19-HYDROXYLASE ENZYMES, THUS INHIBITING SYNTHESIS OF OTHER STEROIDS, INCL ESTROGENS. ...DRUG MAY ALSO DECR PLASMA HALF-LIFE OF CORTISOL, INCR GROWTH HORMONE RELEASE, & INDUCE HYPERGLYCEMIA.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


...DRUG MAY INDUCE ACUTE ADRENAL INSUFFICIENCY IN PT WITH REDUCED ADRENAL SECRETORY CAPACITY. METYRAPONE ALSO INHIBITS SYNTHESIS OF ALDOSTERONE... HOWEVER.../IT/ DOES NOT TYPICALLY CAUSE DEFICIENCY IN MINERALOCORTICOIDS, WITH CONSEQUENT LOSS OF SODIUM & RETENTION OF POTASSIUM...

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


OCCASIONALLY, ARTERIAL BLOOD PRESSURE MAY FALL & MODERATE INCR IN PULSE RATE MAY INSUE. ...SHOULD NOT BE USED IN PT WITH ADRENOCORTICAL INSUFFICIENCY...SAFE USE OF DRUG IN PREGNANCY HAS NOT BEEN ESTABLISHED.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


ABILITY OF ADRENAL TO RESPOND TO ACTH SHOULD BE DEMONSTRATED BEFORE METYRAPONE IS EMPLOYED...

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


For more Drug Warnings (Complete) data for METYRAPONE (8 total), please visit the HSDB record page.


4.4 Drug Indication

Used as a diagnostic drug for testing hypothalamic-pituitary ACTH function. Occasionally used in Cushing's syndrome.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Metopirone is an inhibitor of endogenous adrenal corticosteroid synthesis.


5.2 MeSH Pharmacological Classification

Antimetabolites

Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Antimetabolites.)


Enzyme Inhibitors

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
METYRAPONE
5.3.2 FDA UNII
ZS9KD92H6V
5.3.3 Pharmacological Classes
Adrenal Steroid Synthesis Inhibitors [MoA]; Adrenal Steroid Synthesis Inhibitor [EPC]
5.4 ATC Code

V - Various

V04 - Diagnostic agents

V04C - Other diagnostic agents

V04CD - Tests for pituitary function

V04CD01 - Metyrapone


5.5 Absorption, Distribution and Excretion

Absorption

Absorbed rapidly and well when administered orally. Peak plasma concentrations are usually reached 1 hour after administration.


Route of Elimination

After administration of 4.5 g metyrapone (750 mg every 4 hours), an average of 5.3% of the dose was excreted in the urine in the form of metyrapone (9.2% free and 90.8% as glucuronide) and 38.5% in the form of metyrapol (8.1% free and 91.9% as glucuronide) within 72 hours after the first dose was given.


GASTROINTESTINAL ABSORPTION OF METYRAPONE IS VARIABLE. FOLLOWING ORAL ADMIN OF 750 MG OF METYRAPONE EVERY 4 HR TO NORMAL PT, PEAK PLASMA LEVELS OF ABOUT 1.2 UG M/L...REACHED AFTER THIRD DOSE...0.4 UG/ML...PRESENT IMMEDIATELY AFTER SIXTH DOSE.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


...PLASMA LEVELS OF METYRAPONE...IN RATS WERE SHOWN TO EXHIBIT A CIRCADIAN PATTERN WHEN ANIMALS WERE KEPT IN ALTERNATING 12-HR LIGHT-12 HR DARK REGIMEN. HALF-LIFE...OBSERVED @ 10:00 PM WAS APPROX 2.5 TIMES LONGER THAN THAT OBSERVED @ 10:00 AM...

Testa, B. and P. Jenner. Drug Metabolism: Chemical & Biochemical Aspects. New York: Marcel Dekker, Inc., 1976., p. 408


...WITHIN 2 DAYS FOLLOWING ORAL ADMIN OF 750 MG...EVERY 4 HR FOR 6 DOSES, APPROX 0.5%...IS EXCRETED IN URINE UNCHANGED, 3% IS EXCRETED AS REDUCED METABOLITE, & 37% AS GLUCURONIDE CONJUGATES OF METYRAPONE & ITS METABOLITES.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


5.6 Metabolism/Metabolites

Hepatic. The major biotransformation is reduction of the ketone to metyrapol, an active alcohol metabolite. Metyrapone and metyrapol are both conjugated with glucuronide.


/METYRAPONE IS METABOLIZED BY/ ONE ENZYME, PRESENT IN MICROSOMAL FRACTION OF RAT LIVER, IS NADPH-DEPENDENT & IS ACTIVE UNDER AEROBIC CONDITIONS, REDUCING COMPD TO 2-METHYL-1,2-BIS-(3-PYRIDYL)PROPAN-1-OL...SECOND ENZYME...HAS NOT BEEN IDENTIFIED...

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 372


5.7 Biological Half-Life

1.9 ±0.7 hours.


METYRAPONE HAS PLASMA HALF-LIFE OF ABOUT 20-26 MIN.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 36:66


5.8 Mechanism of Action

The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-ß-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary 17-hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS). Because of these actions, metopirone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Metopirone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.


METYRAPONE REDUCES CORTISOL PRODUCTION BY INHIBITION OF 11BETA-HYDROXYLATION REACTION. BIOSYNTHETIC PROCESS IS TERMINATED @ 11DESOXYCORTISOL... IN NORMAL PERSON...INCR IN ACTH RELEASE FOLLOWS, & SECRETION OF 11DESOXYCORTISOL...ACCELERATED.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1502


ORAL ADMIN OF 250 MG/SQ M BODY SURFACE INCR PLASMA CONCN OF GLUCOSE & GROWTH HORMONE IN CHILDREN.

DAMMACO ET AL; EFFECTS OF ORAL ADMIN OF METYRAPONE ON HUMAN GROWTH HORMONE SECRETION & GLUCOSE METABOLISM IN CHILDREN; BOLL SOC ITAL BIOL SPER 50(6) 1315-320 (1974)


@ LOW DOSES PGE2 & PGF2ALPHA RELEASE WERE STIMULATED. @ HIGHER DOSES PGF2ALPHA RELEASE WAS INHIBITED.

PARNHAM MJ; EFFECTS OF METYRAPONE ON RAT UTERINE PROSTAGLANDIN RELEASE & ON SPONTANEOUS SMOOTH MUSCLE ACTIVITY IN VITRO; BR J PHARMACOL 57(3) 465-466 (1976)