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Metopirone (METYRAPONE)

Esteve · FDA-approved approved Small molecule Quality 60/100

Metopirone works by inhibiting the enzyme responsible for converting a precursor into cortisol, effectively reducing cortisol production.

Metopirone (Metyrapone) is a small molecule adrenal steroid synthesis inhibitor developed by HRA Pharma and currently owned by Esteve. It targets the cytochrome P450 11B1 enzyme in the mitochondria, which is involved in cortisol production. Metopirone is FDA-approved for diagnostic testing of secondary adrenocortical insufficiency since 1961. As an off-patent medication, it is not commercially available as a generic. Metopirone's commercial status and safety considerations require careful evaluation.

At a glance

Generic nameMETYRAPONE
SponsorEsteve
Drug classAdrenal Steroid Synthesis Inhibitor [EPC]
TargetCytochrome P450 11B1, mitochondrial
ModalitySmall molecule
Therapeutic areaMetabolic
PhaseFDA-approved
First approval1961

Mechanism of action

The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-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 marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and 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 diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Me

Approved indications

Common side effects

Key clinical trials

Primary sources

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SourceUsed for
FDA labelMechanism, indications, dosing, boxed warnings, drug interactions
ClinicalTrials.govTrial enrolment, design, endpoints, results

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