Hubbry Logo
MetyraponeMetyraponeMain
Open search
Metyrapone
Community hub
Metyrapone
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Metyrapone
Metyrapone
Metyrapone
View on Wikipedia
from Wikipedia
Metyrapone
Clinical data
Trade namesMetopirone
AHFS/Drugs.comConsumer Drug Information
Pregnancy
category
Routes of
administration		By mouth
ATC code
Pharmacokinetic data
Elimination half-life1.9 ± 0.7 hours
Identifiers
  • 2-methyl-1,2-di(pyridin-3-yl)propan-1-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.188 Edit this at Wikidata
Chemical and physical data
FormulaC14H14N2O
Molar mass226.279 g·mol−1
3D model (JSmol)
  • O=C(c1cccnc1)C(c2cccnc2)(C)C
  • 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 checkY
  • Key:FJLBFSROUSIWMA-UHFFFAOYSA-N checkY
  (verify)

Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). It is part of the steroidogenesis inhibitor class of drugs.

Medical uses

[edit]

Metyrapone can be used in the diagnosis of adrenal insufficiency. Metyrapone 30 mg/kg, maximum dose 3,000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220 nmol/L indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore, if 11-deoxycortisol levels do not rise and remain less than 7 μg/dL (202 nmol/L) and adrenocorticotropic hormone (ACTH) rises, then it is highly suggestive of adrenal insufficiency. If neither 11-deoxycortisol nor ACTH rise, it is highly suggestive of an impaired hypothalamic–pituitary–adrenal axis at either the pituitary or hypothalamus.

The metyrapone test may aid in verifying the cause of Cushing's syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH-producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone.

Metyrapone is used for the medical control of hypercortisolism in Cushing's syndrome (ACTH dependent or independent). The aim for medical treatment is to achieve pre-operative control of hypercortisolism, or for control of residual disease persisting post-operatively (TSS, adrenalectomy). It is not for long term definitive treatment/cure, only as an adjunct (surgery is the aim for cure in most causes of Cushing's syndrome). Metyrapone hence acts by inhibiting adrenal steroidogenesis. One side effect is hirsutism (in women) because of the excess androgen precursors created. The other commonly used agent for medical treatment of Cushing's is ketoconazole (an anti-fungal agent), though it is not FDA approved for Cushing's. This does not exhibit the side effect of hirsutism, but does carry a high risk of hepatoxicity and other serious side effects. Levoketoconazole, an enantiomeric form of ketoconazole, is FDA approved to treat Cushing's and carries a lower risk of hepatoxicity and other serious side effects compared to ketoconazole.

Pharmacology

[edit]

Pharmacodynamics

[edit]

Metyrapone blocks cortisol steroidogenesis by acting as a reversible inhibitor of 11β-hydroxylase.[1] This stimulates adrenocorticotropic hormone (ACTH) secretion, which in turn increases plasma 11-deoxycortisol levels.

Chemistry

[edit]

Analogues of metyrapone include aminoglutethimide, amphenone B, and mitotane.

Research

[edit]

Metyrapone has been found in early human trials to reduce recollection of emotional memories in normal volunteers. The volunteers showed significant impairment in ability to retrieve memories with negative emotional content while not impairing memories with neutral content. This has significant implication in the study of the process of emotional healing in post traumatic stress disorder.[2][3]

Due to the permissive action of cortisol on glucagon, partial blockade of cortisol may reduce the effects of circulating glucagon in chronically increasing blood glucose in metabolic syndrome (syndrome X) and type 2 diabetes.

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Metyrapone

View on Grokipedia
from Grokipedia
Metyrapone, sold under the brand name Metopirone, is a derivative primarily employed as a diagnostic agent to evaluate the function of the hypothalamic-pituitary-adrenocortical (HPA) axis, particularly in differentiating causes of . It functions as a selective inhibitor of the 11β-monooxygenase (also known as 11β-hydroxylase), which blocks the conversion of to in the , thereby reducing and production while stimulating (ACTH) secretion and elevating precursor steroids like . Chemically, metyrapone is 2-methyl-1,2-di-3-pyridyl-1-propanone, a white to light amber crystalline powder with the molecular formula C14H14N2O and a molecular weight of 226.28; it is sparingly soluble in water but soluble in and . Approved by the U.S. in 1961, it is administered orally as 250 mg capsules and exhibits rapid absorption with a plasma of approximately 1.9 hours. Beyond diagnostics, metyrapone is occasionally used off-label in the United States but approved in the for the medical management of , an endocrine disorder characterized by excessive production, especially in cases refractory to or as preoperative to normalize hypercortisolemia. In such therapeutic contexts, it effectively lowers urinary free levels and alleviates symptoms like , , and , with dosages titrated from 250 mg daily up to 6 g per day based on clinical response and monitoring. Long-term use, as demonstrated in case studies spanning several years, has shown good tolerability, though potential adverse effects include , , , gastrointestinal upset, and rare instances of or , necessitating close biochemical surveillance. Contraindicated in patients with known or preexisting adrenal cortical insufficiency, metyrapone remains a cornerstone in for both testing and targeted suppression.

Medical Uses

Diagnostic Applications

Metyrapone is employed in the standard metyrapone stimulation test to evaluate hypothalamic-pituitary-adrenal (HPA) axis integrity, primarily for diagnosing by inhibiting 11β-hydroxylase and assessing the compensatory ACTH response. The protocol involves administering an oral dose of 30 mg/kg body weight (maximum of 3 g) at , ideally with a snack such as to enhance absorption and reduce gastrointestinal upset. Blood samples are collected the following morning at 8:00 AM to measure plasma , 11-deoxycortisol, and ACTH levels, confirming blockade of cortisol synthesis while evaluating pituitary responsiveness. Preparation requires withholding exogenous glucocorticoids for at least 48 hours prior (or longer for longer-acting agents), ensuring normal function, and avoiding medications that induce enzymes (e.g., rifampin), with no overnight fasting necessary. replacement (typically 20-50 mg orally or IV) is administered immediately after sampling to prevent , particularly in patients at risk, and monitoring for symptoms of hypocortisolemia (e.g., , ) is essential during the test. Interpretation hinges on post-stimulation levels: adequate enzyme inhibition is indicated by plasma below 138 nmol/L (5 μg/dL), while a normal pituitary response shows exceeding 202 nmol/L (7 μg/dL) and ACTH rising above 17 pmol/L (75 pg/mL), confirming intact HPA axis function. In secondary (pituitary or hypothalamic origin), both and ACTH responses are blunted ( <202 nmol/L, ACTH <32 pmol/L or 147 pg/mL), reflecting impaired ACTH secretion. The test differentiates primary from secondary : in primary cases, baseline ACTH is markedly elevated (>100 pg/mL) with low , and post-metyrapone remains low due to adrenal unresponsiveness despite high ACTH drive, whereas secondary cases show low or normal baseline ACTH with inadequate post-stimulation increments. This distinction aids in guiding further or etiological investigations.

Therapeutic Applications

Metyrapone is primarily employed in the therapeutic management of to suppress excessive production and alleviate associated symptoms. Treatment typically begins with an initial dose of 250 mg administered three times daily, with upward titration based on urinary free (UFC) levels to achieve biochemical control, reaching a maximum of up to 6 g per day in severe cases. To mitigate the risk of from blockade, metyrapone is frequently combined with exogenous glucocorticoids, such as at replacement doses (e.g., 10-20 mg/day), particularly in block-and-replace regimens where higher metyrapone doses are used. In patients awaiting definitive interventions, metyrapone facilitates preoperative normalization of hypercortisolism to reduce perioperative complications like and , often administered for several weeks to months prior to . It also serves as a bridge in scenarios where is contraindicated or has failed, or when transitioning to for pituitary-dependent disease, providing interim symptom relief and biochemical stabilization. Clinical efficacy data from large cohorts demonstrate that metyrapone reduces levels in over 80% of patients with , with approximately 50-75% achieving eucortisolemia, though the therapy remains palliative and does not address the underlying etiology; a notable is hirsutism in some patients due to accumulation of precursors. Ongoing monitoring is essential and includes weekly UFC or late-night salivary measurements to guide dose adjustments, alongside clinical evaluations for hypoadrenalism symptoms such as , , or imbalances, with prompt supplementation if needed.

Pharmacodynamics

Metyrapone exerts its primary pharmacological effect through reversible inhibition of the 11β-hydroxylase (CYP11B1), a predominantly expressed in the of the . This inhibition competitively blocks the conversion of to in the final step of , thereby reducing production. The mechanism involves coordination of metyrapone's with the iron of CYP11B1, preventing substrate binding and oxygen activation necessary for . The reduction in cortisol levels disrupts negative feedback in the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. Elevated ACTH stimulates the adrenal cortex, resulting in accumulation and increased plasma levels of upstream precursors such as 11-deoxycortisol and deoxycorticosterone, as well as adrenal androgens including dehydroepiandrosterone (DHEA). Furthermore, inhibition of CYP11B1 by metyrapone blocks the synthesis of 11-oxygenated androgens, such as 11-ketotestosterone and 11-hydroxyandrostenedione, in the adrenal gland. However, metyrapone is less potent than osilodrostat in inhibiting CYP11B1 and managing hyperandrogenemia. These changes are measurable as elevated urinary 17-hydroxycorticosteroids and can manifest clinically as hirsutism or acne due to androgen excess in prolonged use. Metyrapone demonstrates relative selectivity for CYP11B1 over aldosterone synthase (CYP11B2), the enzyme responsible for aldosterone production in the , owing to differences in enzyme structure and substrate affinity. Although it can inhibit CYP11B2 at higher concentrations, the impact on aldosterone synthesis is typically minimal under standard dosing, with only mild observed rather than significant deficiency. This selectivity profile helps preserve sodium balance while targeting excess. The degree of enzyme inhibition correlates with plasma metyrapone concentrations in a dose-dependent manner; following a single 2,000 mg oral dose, peak levels of approximately 7.3 μg/mL are achieved, resulting in substantial blockade of cortisol synthesis sufficient for diagnostic testing. At these levels, the ratio of 11-deoxycortisol to cortisol serves as a reliable index of >80-90% inhibition of 11β-hydroxylase activity.

Pharmacokinetics

Metyrapone is rapidly absorbed following , with peak plasma concentrations typically achieved within 1 hour. For example, after a 750 mg dose, mean peak levels reach approximately 3.7 μg/mL, declining to 0.5 μg/mL after 4 hours, while a single 2000 mg dose yields mean peaks of 7.3 μg/mL. The drug distributes throughout the body, crossing the as evidenced by animal studies and at least one human , and it penetrates the blood-brain barrier. Specific quantitative data on and are not well-established in primary pharmacokinetic studies. Metyrapone undergoes hepatic metabolism primarily through reduction of its ketone group to form metyrapol, an active alcohol metabolite, followed by glucuronide conjugation of both parent compound and metabolite. Eight hours post-dose, the plasma ratio of metyrapone to metyrapol is approximately 1:1.5. This metabolic pathway does not involve cytochrome P450 enzymes like CYP3A4 for the reduction step, though metyrapone can induce CYP3A4 expression. Elimination is rapid, with a mean terminal of 1.9 ± 0.7 hours for metyrapone and approximately twice that for metyrapol. The drug and its metabolites are primarily excreted renally, with about 5.3% of a 4.5 g dose (750 mg every 4 hours) recovered as metyrapone (mostly conjugated) and 38.5% as metyrapol (predominantly conjugated) in within 72 hours; less than 1% is excreted unchanged. can be affected by liver impairment, which delays and clearance, while no significant interactions with food have been reported, though administration with meals may mitigate gastrointestinal side effects.

Adverse Effects

Common Adverse Effects

Common adverse effects of metyrapone are typically mild, dose-dependent, and reversible, occurring in approximately 25% of patients in clinical studies, with most resolving upon dose adjustment or discontinuation. Gastrointestinal disturbances represent the most frequent complaints, including , , and or discomfort, affecting up to 23% of patients; these often arise early in treatment or with dose increases and can be mitigated by taking the with or . Overall gastrointestinal issues are reported in 15-25% of cases across studies. Dermatological reactions, particularly and , occur in women, with reported incidences ranging from 4.5% to 71.4%, stemming from elevated precursors due to enzyme inhibition (as detailed in ); these may improve with adjunctive therapy. Neurological effects such as , , drowsiness, and affect 10-15% of users and are usually transient, though patients should avoid or operating machinery until symptoms subside. Additional common effects include rash (incidence around 4%); management generally involves dose reduction or supportive antiemetics for persistent symptoms, with full reversibility expected upon cessation.

Serious Adverse Effects

Metyrapone inhibits cortisol synthesis, which can precipitate hypoadrenalism or , particularly in patients with pre-existing adrenal compromise or during long-term use without adequate replacement. This serious endocrine effect manifests as , severe , , and potentially life-threatening shock if untreated, necessitating prompt co-administration of glucocorticoids such as to prevent or manage . The risk is heightened in individuals with reduced adrenal reserve, where metyrapone exacerbates deficiency, mimicking stress-induced demands on the hypothalamic-pituitary-adrenal axis. Hematological adverse effects are rare but include allergic as a reaction and, infrequently, leading to , , , or profound . These events may require discontinuation of and supportive care, with case reports documenting severe resolving after withdrawal. Cardiovascular risks involve orthostatic hypotension, which can be pronounced in elderly patients due to combined effects of cortisol suppression and potential volume depletion. Overall incidence of these serious effects is low, but risk factors include pre-existing adrenal insufficiency and prolonged therapy; case reports highlight severe hyponatremia as a complication, potentially from electrolyte imbalances during adrenal crisis. Contraindications encompass hypersensitivity to metyrapone and primary adrenocortical insufficiency, while precautions are advised in pregnancy (Category C), where transplacental transfer may impair fetal steroid biosynthesis. Monitoring for signs of adrenal insufficiency, such as electrolyte disturbances, is essential during metyrapone therapy.

Chemistry

Chemical Structure

Metyrapone, with the IUPAC name 2-methyl-1,2-di(pyridin-3-yl)propan-1-one, has the molecular formula C14H14N2O and a of 226.28 g/mol. The features a central group conjugated to one ring at the 3-position, while the adjacent carbon bears two methyl groups and another ring at the 3-position, forming a dimethyl substitution pattern. This arrangement positions the two rings in a manner that facilitates interaction with target enzymes, where the atoms in the rings play a key role in binding by coordinating to the iron. For structural representation, the SMILES notation is CC(C)(c1cccnc1)C(=O)c2cccnc2, which can be used to generate diagrams illustrating the connectivity and . This structural motif enables metyrapone to act as a competitive inhibitor of CYP11B1 by occupying the enzyme's , where the and components mimic aspects of substrates, and the nitrogen directly ligates the iron to block substrate access.

Physicochemical Properties

Metyrapone appears as a white to amber, fine crystalline powder with a characteristic . It darkens upon exposure to . The compound exhibits poor in , approximately 0.43 mg/mL at , but is freely soluble in , , and . This profile, combined with a logP value of approximately 1.8 to 2.1, indicates moderate that influences its formulation and absorption characteristics. Metyrapone is stable under normal storage conditions, remaining viable for at least two years when kept in an inert atmosphere at , though aqueous solutions should not be stored longer than one day. Its pKa is around 4.6 to 4.9, corresponding to the protonation of the moiety. The of metyrapone ranges from 50 to 55°C, which supports its suitability for encapsulation in oral formulations such as 250 mg capsules. Structurally, metyrapone differs from other adrenal steroidogenesis inhibitors like , which features a dichlorodiphenylethane backbone rather than the bis-pyridyl core of metyrapone.

History

Discovery and Development

Metyrapone was developed by the pharmaceutical company Ciba (now part of ) in the mid-1950s as part of efforts to create selective inhibitors of adrenal steroidogenesis, building on earlier work with amphenone analogs that showed adrenocortical inhibitory properties but lacked specificity. Researchers at Ciba, including J.J. , H. Sheppard, M.J. Allen, and W.L. Bencze, synthesized metyrapone (initially designated SU-4885) to target key steps in biosynthesis more precisely. The compound was first described in a 1958 publication in Experientia, where Chart and colleagues reported its potent inhibition of 11β-hydroxylase, a critical in the responsible for converting to . Early preclinical studies in animal models, including dogs and rats, demonstrated that metyrapone administration led to rapid suppression of plasma and urinary levels while increasing precursors like , confirming its mechanism as a competitive inhibitor without affecting earlier steps in steroidogenesis. These findings highlighted metyrapone's utility as a pharmacological tool for probing adrenal function. The development occurred amid a surge in post-World War II research on endocrine disorders, driven by the successful isolation and therapeutic use of adrenal steroids like in the and , which spurred interest in modulating adrenal hormone production to study and treat conditions such as and . A U.S. for metyrapone (No. 2,923,710) was granted to Ciba in 1960, solidifying its intellectual foundation and paving the way for clinical exploration.

Regulatory Approval and Availability

Metyrapone, marketed under the brand name Metopirone, received initial approval from the U.S. (FDA) on December 4, 1961, for diagnostic use in assessing hypothalamic-pituitary (ACTH) function, particularly in the evaluation of . This approval remains its primary indication in the United States, with no formal expansion to therapeutic uses such as treatment, though off-label applications occur under medical supervision. It is classified as a prescription-only medication and is not subject to any controlled substance scheduling. In the , metyrapone has been authorized (via national agencies) since the 1960s for both diagnostic purposes and the medical management of endogenous , supported by observational and retrospective studies demonstrating its efficacy in lowering. The drug is authorized in multiple member states and is available in multiple countries worldwide, though access can vary due to regional regulatory differences and factors. No major withdrawals or restrictions have been imposed, but regulatory bodies monitor its to ensure appropriate clinical oversight. Metyrapone is formulated exclusively as 250 mg oral capsules, with no generic versions currently available or major markets as of 2025. It was originally developed by Ciba (now part of ) and later marketed by HRA Pharma, which was acquired by in 2022 before the rare diseases division—including Metopirone—was divested to Esteve Pharmaceuticals in 2024. Supply interruptions have been reported in certain regions, including during the early due to constraints.

Research

Clinical Investigations in Endocrine Disorders

Early clinical investigations in the established metyrapone's role in the of through its ability to stimulate pituitary ACTH secretion by blocking synthesis, with studies demonstrating reliable increases in urinary 17-hydroxycorticosteroids in responsive patients. For instance, a 1969 study involving 20 patients with validated a rapid oral metyrapone test (0.5 g every hour for six doses) as a sensitive diagnostic tool, showing ACTH responsiveness via plasma assays and distinguishing pituitary-dependent cases. In the 2010s, retrospective multicenter studies confirmed metyrapone's therapeutic efficacy in , with a 2015 analysis of 195 patients reporting normalization in 80% of cases treated with metyrapone monotherapy or , achieving urinary free (UFC) levels within normal ranges over short- and long-term follow-up. This efficacy was attributed to metyrapone's rapid blockade of 11β-hydroxylase, with mean doses of 1.7 g/day leading to sustained hypercortisolism control in 76% of patients at 12 months. The PROMPT trial (NCT02297945), a prospective phase III/IV multicenter study completed in 2020, further evaluated metyrapone in 50 patients with endogenous , demonstrating UFC normalization in 47% and at least 50% reduction in 80% after 12 weeks at mean doses of 1.66 g/day, alongside improvements in and . Recent data through highlight metyrapone's safety in mild autonomous secretion (MACS), a condition involving subtle adrenal hyperfunction. A real-world study of 15 MACS patients treated with evening metyrapone (500 mg at 6 PM and 250 mg at 10 PM) confirmed tolerability over six months, with no adrenal crises and significant reductions in systolic (-17.7 mmHg) and diastolic (-9.9 mmHg) compared to controls, though two patients discontinued due to side effects. Ongoing trials like NCT06106295 continue to assess metyrapone's role in MACS, building on these findings to support its use in non-surgical candidates. In , response rates from the PROMPT trial indicated 47% biochemical remission at 12 weeks, with post-surgical remission enhanced in pretreated patients by stabilizing levels preoperatively. Meta-analyses and comparative reviews underscore metyrapone's superior short-term control over in . A 2021 reported disease control rates of 66% (95% CI: 46-87%) with metyrapone versus 36-46% for , attributing metyrapone's advantage to faster onset (mean 34 days to normalization) and fewer hepatic adverse events in short-term use. A 2022 review reinforced this, noting metyrapone's efficacy in 75-88% of short-term cases compared to 50-70% for , recommending metyrapone for rapid preoperative control due to its predictable dosing and lower risk. Long-term outcomes include occasional pituitary tumor shrinkage in Cushing's disease patients on metyrapone. A 2021 case report documented significant tumor reduction after two months of metyrapone (1 g/day) in a patient with glucocorticoid-positive feedback, suppressing ACTH and cortisol while avoiding apoplexy, suggesting potential for tumor volume decrease in select cases.

Experimental and Off-Label Uses

Metyrapone has been investigated in preclinical and early-phase studies for its potential to modulate emotional memory consolidation through cortisol inhibition, with implications for psychiatric disorders such as post-traumatic stress disorder (PTSD). In a 2011 randomized, double-blind, placebo-controlled study, administration of metyrapone (a double dose of 1 g) prior to memory retrieval significantly reduced the strength of an emotional memory trace for a negative slideshow narrative, with effects persisting up to one year post-administration, as measured by lower recall accuracy and reduced amygdala activation on fMRI. This cortisol-dependent mechanism suggests therapeutic potential in PTSD, where excessive consolidation of traumatic memories contributes to symptom persistence; metyrapone's blockade of glucocorticoid synthesis could weaken fear-associated memories by disrupting reconsolidation during reactivation. Supporting evidence from HPA axis studies in PTSD patients shows metyrapone induces greater ACTH increases and cortisol decreases compared to controls, highlighting altered stress responsivity that may be targeted for memory modulation. In research, pilot studies have explored metyrapone's role in improving insulin sensitivity via suppression, particularly in conditions of mild hypercortisolism linked to metabolic dysregulation. A prospective demonstrated that low-dose evening metyrapone (250-500 mg) improved glucose and insulin sensitivity in patients with mild autonomous , reducing HOMA-IR indices after 6-12 months of treatment. Ongoing clinical trials as of continue to evaluate these effects, including a phase 2 open-label study assessing metyrapone's impact on glycometabolic control and cardiovascular risk factors in mild hypercortisolism (NCT05255900), and another investigating its safety in mild autonomous with metabolic endpoints (NCT07138274). Off-label applications of metyrapone extend to rare cases of ectopic ACTH syndrome, where it has been used for long-term medical management when surgery is not feasible. In a of a with ectopic due to a bronchial , metyrapone (up to 3 g/day) normalized urinary free and ACTH levels over 5 years, with sustained remission after tumor resection. Preclinical studies suggest potential adjunctive use in tumor models, where intratumoral metyrapone administration reduced tumor growth in models by inhibiting tumor-derived synthesis that activates regulatory T cells. These experimental uses are constrained by small sample sizes in most studies, limiting generalizability; for instance, psychiatric trials often involve fewer than 50 participants, increasing risk of type II errors. Metyrapone lacks FDA approval for any therapeutic indications beyond diagnostic testing, remaining off-label for these applications in the United States. Ethical concerns arise from HPA axis manipulation, potentially exacerbating or altering stress responses in vulnerable populations, necessitating careful monitoring in investigational settings.

References

  1. https://go.drugbank.com/drugs/DB01011
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/012911s038lbl.pdf
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3876709/
  4. https://link.springer.com/article/10.1007/s40267-021-00853-y
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC6215797/
  6. https://www.ncbi.nlm.nih.gov/books/NBK278940/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684459/
  8. https://academic.oup.com/jcem/article/100/8/2807/2836065
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC5393433/
  10. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012911s026lbl.pdf
  11. https://pubmed.ncbi.nlm.nih.gov/14065107/
  12. https://pubmed.ncbi.nlm.nih.gov/17336940/
  13. https://journals.physiology.org/doi/full/10.1152/ajpendo.00418.2005
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC9578081/
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC10757358/
  16. https://link.springer.com/article/10.1007/s11102-016-0742-1
  17. https://academic.oup.com/jcem/article/40/2/290/2684872
  18. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012911Orig1s033lbl.pdf
  19. https://onlinelibrary.wiley.com/doi/10.1111/jne.13118
  20. https://pubmed.ncbi.nlm.nih.gov/10917608/
  21. https://www.drugs.com/monograph/metyrapone.html
  22. https://www.mayoclinic.org/drugs-supplements/metyrapone-oral-route/description/drg-20067784
  23. https://www.mayoclinic.org/drugs-supplements/metyrapone-oral-route/side-effects/drg-20067784
  24. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1060884/full
  25. https://www.sciencedirect.com/topics/medicine-and-dentistry/metyrapone
  26. https://www.drugs.com/pro/metopirone.html
  27. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.21519
  28. https://link.springer.com/article/10.1007/s40278-020-80409-0
  29. https://pubchem.ncbi.nlm.nih.gov/compound/Metyrapone
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC1564212/
  31. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0773.1998.tb01473.x
  32. https://drugcentral.org/drugcard/1791
  33. https://www.chemicalbook.com/ProductChemicalPropertiesCB8329426_EN.htm
  34. https://www.lookchem.com/casno54-36-4.html
  35. https://www.sigmaaldrich.com/US/en/product/sigma/m2696
  36. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8329426.htm
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC9835964/
  38. https://cdek.pharmacy.purdue.edu/api/47929/
  39. https://www.drugs.com/cons/metyrapone.html
  40. https://pmc.ncbi.nlm.nih.gov/articles/PMC8090655/
  41. https://www.ema.europa.eu/en/medicines/psusa/psusa-00002046-202406
  42. https://www.drugs.com/availability/generic-metopirone.html
  43. https://investor.perrigo.com/2022-05-02-PERRIGO-COMPLETES-THE-ACQUISITION-OF-HRA-PHARMA
  44. https://www.esteve.com/uk/media/news/esteve-acquires-hra-pharma-rare-diseases
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC8881150/
Add your contribution
Related Hubs
User Avatar
No comments yet.