METYRAPONE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H14N2O.2C4H6O6
Molecular Weight	526.4474
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.CC(C)(C(=O)C1=CC=CN=C1)C2=CC=CN=C2

InChI

InChIKey=FBSAWAHQGRDEJD-WBPXWQEISA-N

InChI=1S/C14H14N2O.2C4H6O6/c1-14(2,12-6-4-8-16-10-12)13(17)11-5-3-7-15-9-11;2*5-1(3(7)8)2(6)4(9)10/h3-10H,1-2H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t;2*1-,2-/m.11/s1

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

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf | https://www.drugs.com/cdi/metyrapone.html

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 11B1 9 Target ID: CHEMBL1908 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf \| https://www.drugbank.ca/drugs/DB01011 \| https://www.ncbi.nlm.nih.gov/pubmed/21129965	Inhibitor 8504		14.6 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Secondary adrenocortical insufficiency 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf http://adisinsight.springer.com/drugs/800035568	Diagnostic		Approved 8583	METOPIRONE Approved Use Metopirone is a diagnostic drug for testing hypothalamic‑pituitary ACTH function. Launch Date 1961

C_max

Value	Dose	Co-administered	Analyte	Population
3.7 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf	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
7.3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf	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

Doses

Dose	Population	Adverse 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012911s036lbl.pdf	unknown, 6 years Health Status: unknown Age Group: 6 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012911s036lbl.pdf	Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (acute) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012911s036lbl.pdf
1600 mg 1 times / day steady, oral Dose: 1600 mg, 1 times / day Route: oral Route: steady Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26353009	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26353009	Disc. AE: Gastrointestinal upset, Dizziness... AEs leading to discontinuation/dose reduction: Gastrointestinal upset (23%) Dizziness (23%) Sources: https://pubmed.ncbi.nlm.nih.gov/26353009

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012911s036lbl.pdf	unknown, 6 years Health Status: unknown Age Group: 6 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/012911s036lbl.pdf
Dizziness	23% Disc. AE	1600 mg 1 times / day steady, oral Dose: 1600 mg, 1 times / day Route: oral Route: steady Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26353009	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26353009
Gastrointestinal upset	23% Disc. AE	1600 mg 1 times / day steady, oral Dose: 1600 mg, 1 times / day Route: oral Route: steady Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26353009	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26353009

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252 substrate 1946		inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP11B1 10 OATP1B1 1079 OATP1B3 961

Drug as perpetrator

Target	Modality	Activity
OATP1B1 1095	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376123/pdf/nihms47229.pdf Page: 11.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376123/pdf/nihms47229.pdf Page: 11.0	no
CYP11B1 10	inhibitor 4027 Sources: https://link.springer.com/article/10.1016/S1734-1140(10)70363-7 Page: 5.0	yes
CYP2D6 2546	inhibitor 4027 Sources: https://link.springer.com/article/10.1016/S1734-1140(10)70363-7 Page: 5.0	yes
CYP3A4 2633	inducer 1966 Sources: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2265.2011.04214.x Page: 4.0	yes
CYP3A4 2633	inhibitor 4027 Sources: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2265.2011.04214.x Page: 4.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.mdpi.com/2218-273X/10/1/112 Page: 7.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:44241	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:44241
ChemicalBook	CB8329426	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8329426
eMolecules	531552	https://www.emolecules.com/cgi-bin/more?vid=531552
MolPort	MolPort-001-794-644	https://www.molport.com/shop/molecule-link/MolPort-001-794-644
ZINC	ZINC000000001728	http://zinc15.docking.org/substances/ZINC000000001728

PubMed

Title	Date	PubMed
Exposure of brown trout Salmo trutta to a sublethal concentration of copper in soft acidic water: effects upon gas exchange and ammonia accumulation.	2003-01	12456705
Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice.	2002-12	12442337
Cushing's syndrome during pregnancy: curative adrenalectomy at 31 weeks gestation.	2002-11-15	12381486
Leukemia inhibitory factor is a mediator of Escherichia coli lipopolysaccharide-induced acute thymic atrophy.	2002-11	12385026
The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism.	2002-10	12372848
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.	2002-10	12364444
Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids.	2002-10	12297537
Does cortisol mediate endotoxin-induced inhibition of pulsatile luteinizing hormone and gonadotropin-releasing hormone secretion?	2002-10	12239084
Determination of the plasma levels of metyrapone and its enantiomeric metyrapol metabolites by direct plasma injection and multidimensional achiral-chiral chromatography.	2002-10	12237834
The contribution of cytochrome P-450 isoenzymes to the metabolism of phenothiazine neuroleptics.	2002-10	12208554
Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome P450cam and chloroperoxidase.	2002-09-20	12237224
Preirradiation endocrinopathies in pediatric brain tumor patients determined by dynamic tests of endocrine function.	2002-09-01	12182973
Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pig.	2002-09	12193221
Metyrapone-induced corticosterone deficiency impairs glucose oxidation and steroidogenesis in Leydig cells of adult albino rats.	2002-08	12402971
Evidence that metyrapone can act as a stressor: effect on pituitary-adrenal hormones, plasma glucose and brain c-fos induction.	2002-08	12270045
Bench-to-bedside review: a possible resolution of the glucose paradox of cerebral ischemia.	2002-08	12225609
Target cells for cytochrome p450-catalysed irreversible binding of 7,12-dimethylbenz[a]anthracene (DMBA) in rodent adrenal glands.	2002-08	12185414
Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids.	2002-08	12161513
Deoxysarpagine hydroxylase--a novel enzyme closing a short side pathway of alkaloid biosynthesis in Rauvolfia.	2002-08	12057637
The role of cortisol suppression on craving for and satisfaction from nicotine in high and low impulsive subjects.	2002-07	12404678
Brain HSP70 mRNA expression is linked with plasma cortisol levels in goldfish (Carassius auratus) exposed to a potential predator.	2002-07	12149573
Metyrapone for Cushing's syndrome.	2002-07	12091216
Functional scintigraphy of the adrenal gland.	2002-07	12088915
Small changes in whole-body corticosterone content affect larval Rana pipiens fitness components.	2002-06-01	12161197
Erratum to "CNS drugs in Cushing's disease: pathophysiological and therapeutic implications for mood disorders" [Prog. Neuro-Psycol. Biol. Psychiatry, 26, 763 (2002)].	2002-06	12369251
Glucocorticoid replacement in pituitary surgery: guidelines for perioperative assessment and management.	2002-06	12050244
The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.	2002-06	12021197
Ectopic ACTH-syndrome due to a thymic carcinoid tumor.	2002-05-23	12017752
Transcriptional activation of cytochrome P450 CYP2C45 by drugs is mediated by the chicken xenobiotic receptor (CXR) interacting with a phenobarbital response enhancer unit.	2002-05-03	11867618
Residual symptoms in depression an emerging therapeutic concept.	2002-05	12188108
Evidence for glucose-6-phosphate transport in rat liver microsomes.	2002-04-24	12062448
Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice.	2002-04-01	11844579
The low-dose ACTH test does not provide a useful assessment of the hypothalamic-pituitary-adrenal axis in secondary adrenal insufficiency.	2002-04	11966747
Sympathetic nervous system plays a major role in acute cold/restraint stress inhibition of host resistance to Listeria monocytogenes.	2002-04	11960645
The oxidative biotransformation of losoxantrone (CI-941).	2002-04	11901102
Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line.	2002-04	11869873
The modulatory effects of corticosteroids on cognition: studies in young human populations.	2002-04	11818174
Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis.	2002-03	11889204
Induction of cardiac cytochrome p450 in cocaine-treated mice.	2002-03	11856816
Glucocorticoid involvement in memory formation in a rat model for traumatic memory.	2002-02	12171770
Production of carbon monoxide by cytochrome P450 during iron-dependent lipid peroxidation.	2002-02	11812634
Reductive metabolism of p,p'-DDT and o,p'-DDT by rat liver cytochrome P450.	2002-02	11792678
Biosynthesis of beta-substituted furan skeleton in the lower furanoterpenoids: a model study.	2002-01-11	11779213
A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.	2002-01	11845997
Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats.	2002-01	11771941
Evidence that RDX biodegradation by Rhodococcus strain DN22 is plasmid-borne and involves a cytochrome p-450.	2002	12174045
Metabolism of territrem a by liver microsomes of Wistar rats: identification of the metabolites and their metabolic sequence.	2001-12-07	11760155
Rational, effective metyrapone treatment of ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH).	2001-12	11873864
Involvement of adrenal and thyroid activity in the annual testicular regression of red headed bunting (Emberiza bruniceps).	2001-07	12017256
[Pituitary function after transsphenoidal surgery for pituitary adenoma].	2001	11868239

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 17:48:58 GMT 2025` Edited by `admin` on `Mon Mar 31 17:48:58 GMT 2025`
Record UNII	B6DRB5ZI7P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METOPIRONE DITARTRATE

Preferred Name

English

METYRAPONE TARTRATE

Official Name

English

Metyrapone tartrate [WHO-DD]

Common Name

English

METYRAPONE TARTRATE [USAN]

Common Name

English

1-PROPANONE, 2-METHYL-1,2-DI-3-PYRIDINYL-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:2)

Common Name

English

SU-4885

Code

English

2-Methyl-1,2-di-3-pyridyl-1-propanone tartrate (1:2)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471