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Details

Stereochemistry ACHIRAL
Molecular Formula C14H14N2O
Molecular Weight 226.2738
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METYRAPONE

SMILES

CC(C)(C(=O)C1=CN=CC=C1)C2=CC=CN=C2

InChI

InChIKey=FJLBFSROUSIWMA-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C14H14N2O
Molecular Weight 226.2738
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Metyrapone (trade name Metopirone) is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). Metopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteroid synthesis, available as 250-mg capsules for oral administration. The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-β-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.

Originator

Curator's Comment: # Novartis

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Diagnostic
METOPIRONE

Approved Use

Metopirone is a diagnostic drug for testing hypothalamic‑pituitary ACTH function.

Launch Date

-2.54880006E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.7 μg/mL
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
255.5 ng/mL
50 mg/kg single, oral
dose: 50 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7.3 μg/mL
2000 mg single, oral
dose: 2000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
219.6 ng × h/mL
50 mg/kg single, oral
dose: 50 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.9 h
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
0.99 h
50 mg/kg single, oral
dose: 50 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METYRAPONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2 g 2 times / day steady, oral
Overdose
Dose: 2 g, 2 times / day
Route: oral
Route: steady
Dose: 2 g, 2 times / day
Sources:
unknown, 6 years
n = 1
Health Status: unknown
Age Group: 6 years
Sex: F
Population Size: 1
Sources:
Other AEs: Toxic reaction (NOS)...
1600 mg 1 times / day steady, oral (mean)
Dose: 1600 mg, 1 times / day
Route: oral
Route: steady
Dose: 1600 mg, 1 times / day
Sources:
unhealthy
n = 48
Health Status: unhealthy
Condition: Cushing's Syndrome
Population Size: 48
Sources:
Disc. AE: Gastrointestinal upset, Dizziness...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal upset (23%)
Dizziness (23%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Toxic reaction (NOS) acute
2 g 2 times / day steady, oral
Overdose
Dose: 2 g, 2 times / day
Route: oral
Route: steady
Dose: 2 g, 2 times / day
Sources:
unknown, 6 years
n = 1
Health Status: unknown
Age Group: 6 years
Sex: F
Population Size: 1
Sources:
Dizziness 23%
Disc. AE
1600 mg 1 times / day steady, oral (mean)
Dose: 1600 mg, 1 times / day
Route: oral
Route: steady
Dose: 1600 mg, 1 times / day
Sources:
unhealthy
n = 48
Health Status: unhealthy
Condition: Cushing's Syndrome
Population Size: 48
Sources:
Gastrointestinal upset 23%
Disc. AE
1600 mg 1 times / day steady, oral (mean)
Dose: 1600 mg, 1 times / day
Route: oral
Route: steady
Dose: 1600 mg, 1 times / day
Sources:
unhealthy
n = 48
Health Status: unhealthy
Condition: Cushing's Syndrome
Population Size: 48
Sources:
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Biology of posttraumatic stress disorder.
2001
Isolation and characterization of two aerobic bacterial strains that completely degrade ethyl tert-butyl ether (ETBE).
2001 Apr
Glucocorticoid and mineralocorticoid receptors are involved in the facilitation of anxiety-like response induced by restraint.
2001 Apr
Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry.
2001 Apr
Metabolism of territrem a by liver microsomes of Wistar rats: identification of the metabolites and their metabolic sequence.
2001 Dec 7
Bioactivation to free radicals and cytotoxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b).
2001 Feb
A novel drug-regulated gene expression system based on the nuclear receptor constitutive androstane receptor (CAR).
2001 Feb
Irreversible binding and adrenocorticolytic activity of the DDT metabolite 3-methylsulfonyl-DDE examined in tissue-slice culture.
2001 Feb
Pathogenesis of carbon tetrachloride-induced hepatocyte injury bioactivation of CCI4 by cytochrome P450 and effects on lipid homeostasis.
2001 Jan-Feb
Prodissociative effects of metyrapone.
2001 Jul
Role of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus snake venom, on inflammatory and immune reactions.
2001 Jun
Altered HPA axis responsivity to metyrapone testing in methadone maintained former heroin addicts with ongoing cocaine addiction.
2001 May
Corticotropin secretory dynamics in humans under low glucocorticoid feedback.
2001 Nov
The role of adrenal corticosteroids in induction of micronuclei by morphine.
2001 Nov 15
No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: a pilot study.
2001 Oct
Evidence for glucose-6-phosphate transport in rat liver microsomes.
2002 Apr 24
Metyrapone-induced corticosterone deficiency impairs glucose oxidation and steroidogenesis in Leydig cells of adult albino rats.
2002 Aug
Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice.
2002 Dec
Glucocorticoid involvement in memory formation in a rat model for traumatic memory.
2002 Feb
A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.
2002 Jan
Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats.
2002 Jan
The role of cortisol suppression on craving for and satisfaction from nicotine in high and low impulsive subjects.
2002 Jul
Metyrapone for Cushing's syndrome.
2002 Jul
Functional scintigraphy of the adrenal gland.
2002 Jul
Transcriptional activation of cytochrome P450 CYP2C45 by drugs is mediated by the chicken xenobiotic receptor (CXR) interacting with a phenobarbital response enhancer unit.
2002 May 3
The stimulatory effect of canrenoate, a mineralocorticoid antagonist, on the activity of the hypothalamus-pituitary-adrenal axis is abolished by alprazolam, a benzodiazepine, in humans.
2002 Oct
Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids.
2002 Oct
Exposure of brown trout Salmo trutta to a sublethal concentration of copper in soft acidic water: effects upon gas exchange and ammonia accumulation.
2003 Jan
Patents

Patents

Sample Use Guides

Single-Dose Short Test This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH levels after a single dose of Metopirone (Metyrapone). The patient is given 30 mg/kg (maximum 3 g Metopirone) at midnight with yogurt or milk. The same dose is recommended in children. The blood sample for the assay is taken early the following morning (7:30-8:00 a.m.). The plasma should be frozen as soon as possible. The patient is then given a prophylactic dose of 50 mg cortisone acetate. Multiple-Dose Test Day 1: Control period - Collect 24-hour urine for measurement of 17-OHCS or 17-KGS. Day 2: ACTH test to determine the ability of adrenals to respond - Standard ACTH test such as infusion of 50 units ACTH over 8 hours and measurement of 24-hour urinary steroids. If results indicate adequate response, the Metopirone test may proceed. Day 3-4: Rest period. Day 5: Administration of Metopirone: Recommended with milk or snack. Adults: 750 mg orally, every 4 hours for 6 doses. A single dose is approximately equivalent to 15 mg/kg. Children: 15 mg/kg orally every 4 hours for 6 doses. A minimal single dose of 250 mg is recommended. Day 6: After administration of Metopirone - Determination of 24-hour urinary steroids for effect.
Route of Administration: Oral
Metyrapone (IC50) of 1 uM) inhibited the apparent CYP11B1 activity in the H295R human adrenocortical carcinoma cell line.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:19:41 UTC 2023
Edited
by admin
on Fri Dec 15 16:19:41 UTC 2023
Record UNII
ZS9KD92H6V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METYRAPONE
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
METOPIRONE
Brand Name English
METYRAPONE [MART.]
Common Name English
METYRAPONE [HSDB]
Common Name English
METYRAPONE [USP MONOGRAPH]
Common Name English
2-Methyl-1,2-di-3-pyridyl-1-propanone
Systematic Name English
Metyrapone [WHO-DD]
Common Name English
METYRAPONE [VANDF]
Common Name English
metyrapone [INN]
Common Name English
METYRAPONE [ORANGE BOOK]
Common Name English
METYRAPONE [USP-RS]
Common Name English
1-PROPANONE, 2-METHYL-1,2-DI-3-PYRIDINYL-
Systematic Name English
NSC-25265
Code English
METYRAPONE [JAN]
Common Name English
METYRAPONE [USAN]
Common Name English
METYRAPONE [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175921
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
WHO-ATC V04CD01
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
FDA ORPHAN DRUG 377212
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
NDF-RT N0000175928
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
NCI_THESAURUS C471
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
WHO-VATC QV04CD01
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
Code System Code Type Description
ECHA (EC/EINECS)
200-206-2
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
NCI_THESAURUS
C47619
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
PUBCHEM
4174
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PRIMARY
RS_ITEM_NUM
1443001
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PRIMARY
DRUG BANK
DB01011
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
WIKIPEDIA
METYRAPONE
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
FDA UNII
ZS9KD92H6V
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
NSC
25265
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
ChEMBL
CHEMBL934
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PRIMARY
CHEBI
44241
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PRIMARY
MESH
D008797
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PRIMARY
INN
1404
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PRIMARY
SMS_ID
100000092415
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PRIMARY
EVMPD
SUB08925MIG
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PRIMARY
DAILYMED
ZS9KD92H6V
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
IUPHAR
5224
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
HSDB
2500
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
DRUG CENTRAL
1791
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
CAS
54-36-4
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
EPA CompTox
DTXSID1023314
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
MERCK INDEX
m7508
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY Merck Index
RXCUI
6923
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY RxNorm
LACTMED
Metyrapone
Created by admin on Fri Dec 15 16:19:41 UTC 2023 , Edited by admin on Fri Dec 15 16:19:41 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
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