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Chemical Compound Review

Metopiron     2-methyl-1,2-dipyridin-3-yl- propan-1-one

Synonyms: Metopirone, metyrapone, Methopyrapone, Methbipyranone, Su 4885, ...
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Disease relevance of Metopirone

  • Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency [1].
  • When the criteria for both the metyrapone and dexamethasone tests were combined to identify patients with the pituitary Cushing syndrome, the sensitivity and diagnostic accuracy improved to 88% and 89%, respectively [2].
  • Additional clinical features included hypokalemia in six patients and glucocorticoid response to either high-dose dexamethasone or metyrapone in 6 of 13 [3].
  • Metyrapone-induced anosmia was restricted to the pheromone detectors in P. diversa, which became insensitive to physiological concentrations of pheromones for a few minutes [4].
  • Metyrapone-induced hypertension in dogs could be sustained for up to 6 weeks by increased output with no evidence of "autoregulation" developing, and similar observations were reported in some anephric patients [5].

Psychiatry related information on Metopirone


High impact information on Metopirone


Chemical compound and disease context of Metopirone


Biological context of Metopirone

  • Since the only pharmacological property CO and metyrapone are thought to have in common at the concentrations employed is the ability to bind to the heme iron of cytochrome P-450, these results are consistent with the hypothesis that desaturation of this cytochrome leads to pulmonary vasoconstriction [18].
  • Induction of reporter gene activity was blocked when the TEC and reporter cells were incubated in the presence of the Cyp11B1 inhibitor metyrapone or the 3betaHSD inhibitor trilostane, as well as by the GR antagonist RU486 [19].
  • The DNA methylation of NNK catalyzed by all three microsomal systems was inhibited by cytochrome P-450 inhibitors, such as carbon monoxide and metyrapone, but not by the cyclooxygenase inhibitor, aspirin, or by prolonged preincubation in the absence of NADPH [20].
  • A study of the single turnover kinetics of the reaction between oxycytochrome P-450cam and reduced putidaredoxin was performed using the inhibitor metyrapone to trap the cytochrome immediately after release of the product, 5-exo-hydroxycamphor [21].
  • In contrast, the cytochrome P-450 epoxygenase inhibitors, SKF525A and metyrapone, substantially reduced arachidonic acid-induced recovery of growth while having minimal effects on control cell growth [22].

Anatomical context of Metopirone


Associations of Metopirone with other chemical compounds

  • Neither metapyrone (SKF 525A) nor cyanide, inhibitors of cytochrome P-450, inhibited compound A formation, suggesting that a cytochrome P-450 system was not involved [27].
  • Treatment of the perfused segment (but not the bioassay ring) with inhibitors of phospholipase A2 (quinacrine) or cytochrome P450 (metyrapone) had no effect on the basal relaxing activity of the effluent; treatment with the inhibitor of lipoxygenase, nordihydroguaiaretic acid, significantly depressed it [28].
  • This last effect of ACTH was concentration-dependently abolished by both aminoglutethimide and cyanoketone, which blocks early steps of steroid synthesis, but not by metyrapone, an inhibitor of 11beta-hydroxylase [29].
  • By means of molecular dynamics simulations with the newly developed force field parameters for the heme-thiolate group and its dioxygen adduct, we examine the differences in structural and dynamic properties between CYP3A4 in the resting form and its complexes with the substrate progesterone and the inhibitor metyrapone [30].
  • METHODS: Therefore, we quantified the concentrations of an array of neuroactive steroids following administration of 1.5 g metyrapone before and after pretreatment with 1 mg dexamethasone in 19 patients suffering from severe depression in comparison to 13 healthy controls by means of a highly sensitive gas chromatography/mass spectrometry analysis [31].

Gene context of Metopirone

  • In contrast, the activity of CYP2A6 was only weakly inhibited by metyrapone or methoxsalen (ID50 > 50 microM) [32].
  • After metyrapone, CYP11B1/CYP11B2-IR was induced in the DZ and was up-regulated in the TZ and FZ [33].
  • The relative abundance of the mRNAs encoding IGF-II and the IGF-IR was increased after metyrapone treatment, whereas the localization and relative abundance of IGFBP 1-6 mRNAs were not altered by metyrapone treatment [34].
  • Effect of the adrenal 11-beta-hydroxylase inhibitor metyrapone on human hepatic cytochrome P-450 expression: induction of cytochrome P-450 3A4 [35].
  • The adrenostatic compound metyrapone, an inhibitor of 11beta-hydroxylase activity, also suppressed ACTH-R mRNA expression in a similar fashion [36].

Analytical, diagnostic and therapeutic context of Metopirone


  1. Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency. Dolman, L.I., Nolan, G., Jubiz, W. JAMA (1979) [Pubmed]
  2. The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. Avgerinos, P.C., Yanovski, J.A., Oldfield, E.H., Nieman, L.K., Cutler, G.B. Ann. Intern. Med. (1994) [Pubmed]
  3. The Cushing syndrome induced by bronchial carcinoid tumors. Limper, A.H., Carpenter, P.C., Scheithauer, B., Staats, B.A. Ann. Intern. Med. (1992) [Pubmed]
  4. Pheromone anosmia in a scarab beetle induced by in vivo inhibition of a pheromone-degrading enzyme. Maïbèche-Coisne, M., Nikonov, A.A., Ishida, Y., Jacquin-Joly, E., Leal, W.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Hemodynamic role of extracellular fluid in hypertension. Tarazi, R.C. Circ. Res. (1976) [Pubmed]
  6. Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone. Otte, C., Muhtz, C., Daneshkhah, S., Yassouridis, A., Kiefer, F., Wiedemann, K., Kellner, M. Biol. Psychiatry (2006) [Pubmed]
  7. Metyrapone tests in patients with panic disorder. Kellner, M., Schick, M., Yassouridis, A., Struttmann, T., Wiedemann, K., Alm, B. Biol. Psychiatry (2004) [Pubmed]
  8. Declarative memory after stress in humans: differential involvement of the beta-adrenergic and corticosteroid systems. Maheu, F.S., Joober, R., Lupien, S.J. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  9. Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids. Lupien, S.J., Wilkinson, C.W., Brière, S., Ng Ying Kin, N.M., Meaney, M.J., Nair, N.P. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  10. Sleep endocrine effects of the 11-beta-hydroxysteroiddehydrogenase inhibitor metyrapone. Jahn, H., Kiefer, F., Schick, M., Yassouridis, A., Steiger, A., Kellner, M., Wiedemann, K. Sleep. (2003) [Pubmed]
  11. Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration. Nakao, K., Nakai, Y., Oki, S., Horii, K., Imura, H. J. Clin. Invest. (1978) [Pubmed]
  12. Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial. Jahn, H., Schick, M., Kiefer, F., Kellner, M., Yassouridis, A., Wiedemann, K. Arch. Gen. Psychiatry (2004) [Pubmed]
  13. Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone. Lisansky, J., Peake, G.T., Strassman, R.J., Qualls, C., Meikle, A.W., Risch, S.C., Fava, G.A., Zownir-Brazis, M., Hochla, P., Britton, D. Arch. Gen. Psychiatry (1989) [Pubmed]
  14. Cushing's disease in a patient with a 'nonfunctioning' pituitary tumor. Spontaneous development and remission. Gogel, E.L., Salber, P.R., Tyrrell, J.B., Rosenblum, M.L., Findling, J.W. Arch. Intern. Med. (1983) [Pubmed]
  15. Atypical adrenal insufficiency with failure of the pituitary feedback receptor. A case with associated diabetes mellitus and selective IgA deficiency with steatorrhea. Hagen, G.A., Bolman, R.M., Frank, J.P. Am. J. Med. (1975) [Pubmed]
  16. Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin. Nielsen, H.K., Brixen, K., Kassem, M., Charles, P., Mosekilde, L. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  17. Studies of ACTH secretion control in 116 cases of Cushing's syndrome. Raux, M.C., Binoux, M., Luton, J.P., Gourmelen, M., Girard, F. J. Clin. Endocrinol. Metab. (1975) [Pubmed]
  18. The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction. Sylvester, J.T., McGowan, C. Circ. Res. (1978) [Pubmed]
  19. Paracrine glucocorticoid activity produced by mouse thymic epithelial cells. Pazirandeh, A., Xue, Y., Rafter, I., Sjövall, J., Jondal, M., Okret, S. FASEB J. (1999) [Pubmed]
  20. Metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone as measured by DNA alkylation in vitro and its inhibition by isothiocyanates. Guo, Z., Smith, T.J., Thomas, P.E., Yang, C.S. Cancer Res. (1991) [Pubmed]
  21. Single turnover kinetics of the reaction between oxycytochrome P-450cam and reduced putidaredoxin. Brewer, C.B., Peterson, J.A. J. Biol. Chem. (1988) [Pubmed]
  22. Recovery of Ca2+ pools and growth in Ca2+ pool-depleted cells is mediated by specific epoxyeicosatrienoic acids derived from arachidonic acid. Graber, M.N., Alfonso, A., Gill, D.L. J. Biol. Chem. (1997) [Pubmed]
  23. Cytotoxicity of mitomycin C and adriamycin in freshly isolated rat hepatocytes: the role of cytochrome P450. Goeptar, A.R., Groot, E.J., Scheerens, H., Commandeur, J.N., Vermeulen, N.P. Cancer Res. (1994) [Pubmed]
  24. Inhibition of cortisol production with metyrapone prevents mental stress-induced endothelial dysfunction and baroreflex impairment. Broadley, A.J., Korszun, A., Abdelaal, E., Moskvina, V., Jones, C.J., Nash, G.B., Ray, C., Deanfield, J., Frenneaux, M.P. J. Am. Coll. Cardiol. (2005) [Pubmed]
  25. Pituitary function after removal of pituitary microadenomas in Cushing's disease. Schnall, A.M., Brodkey, J.S., Kaufman, B., Pearson, O.H. J. Clin. Endocrinol. Metab. (1978) [Pubmed]
  26. Metyrapone, an inhibitor of glucocorticoid production, reduces brain injury induced by focal and global ischemia and seizures. Smith-Swintosky, V.L., Pettigrew, L.C., Sapolsky, R.M., Phares, C., Craddock, S.D., Brooke, S.M., Mattson, M.P. J. Cereb. Blood Flow Metab. (1996) [Pubmed]
  27. Formation of cis-14,15-oxido-5,8,11-icosatrienoic acid from phosphatidylinositol in human platelets. Ballou, L.R., Lam, B.K., Wong, P.Y., Cheung, W.Y. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  28. Nature of endothelium-derived relaxing factor: are there two relaxing mediators? Rubanyi, G.M., Vanhoutte, P.M. Circ. Res. (1987) [Pubmed]
  29. 11beta-hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex. Mazzocchi, G., Rossi, G.P., Neri, G., Malendowicz, L.K., Albertin, G., Nussdorfer, G.G. FASEB J. (1998) [Pubmed]
  30. Structural and dynamical basis of broad substrate specificity, catalytic mechanism, and inhibition of cytochrome P450 3A4. Park, H., Lee, S., Suh, J. J. Am. Chem. Soc. (2005) [Pubmed]
  31. Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers. Rupprecht, R., Ströhle, A., Hermann, B., di Michele, F., Spalletta, G., Pasini, A., Holsboer, F., Romeo, E. Biol. Psychiatry (1998) [Pubmed]
  32. Baculovirus-mediated expression and characterization of rat CYP2A3 and human CYP2a6: role in metabolic activation of nasal toxicants. Liu, C., Zhuo, X., Gonzalez, F.J., Ding, X. Mol. Pharmacol. (1996) [Pubmed]
  33. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Coulter, C.L., Jaffe, R.B. Endocrinology (1998) [Pubmed]
  34. Functional maturation of the primate fetal adrenal in vivo: I. Role of insulin-like growth factors (IGFs), IGF-I receptor, and IGF binding proteins in growth regulation. Coulter, C.L., Goldsmith, P.C., Mesiano, S., Voytek, C.C., Martin, M.C., Han, V.K., Jaffe, R.B. Endocrinology (1996) [Pubmed]
  35. Effect of the adrenal 11-beta-hydroxylase inhibitor metyrapone on human hepatic cytochrome P-450 expression: induction of cytochrome P-450 3A4. Harvey, J.L., Paine, A.J., Maurel, P., Wright, M.C. Drug Metab. Dispos. (2000) [Pubmed]
  36. Aminoglutethimide suppresses adrenocorticotropin receptor expression in the NCI-h295 adrenocortical tumor cell line. Fassnacht, M., Beuschlein, F., Vay, S., Mora, P., Allolio, B., Reincke, M. J. Endocrinol. (1998) [Pubmed]
  37. Hormone secretion in alcohol-induced pseudo-Cushing's syndrome. Differential diagnosis with Cushing disease. Lamberts, S.W., Klijn, J.G., de Jong, F.H., Birkenhäger, J.C. JAMA (1979) [Pubmed]
  38. Multifactorial analysis of chronic hypertension induced by electrolyte-active steroids in trained, unanesthetized dogs. Bravo, E.L., Tarazi, R.C., Dustan, H.P. Circ. Res. (1977) [Pubmed]
  39. Electroconvulsive therapy for iatrogenic hypothalamic-hypopituitarism (CRF-ACTH type). Pitts, F.N., Patterson, C.W. The American journal of psychiatry. (1979) [Pubmed]
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