|Synonyms||Methyltrienolone, 17α-Methyltrenbolone; R1881; R-1881; RU-1881; NSC-92858; 17α-Methyl-19-nor-Δ9,11-testosterone; 17α-Methylestra-4,9,11-trien-17β-ol-3-one|
|Chemical and physical data|
|Molar mass||284.393 g/mol|
|3D model (JSmol)|
|(what is this?)|
Metribolone (developmental code name R1881), also known as methyltrienolone, is an orally active anabolic-androgenic steroid (AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for medical use but has been widely used in scientific research as a hot ligand in androgen receptor (AR) ligand binding assays (LBAs) and as a photoaffinity label for the AR. It was investigated briefly for the treatment of advanced breast cancer in women in the late 1960s and early 1970s but was found to produce signs of severe hepatotoxicity at very low dosages, and its development was subsequently discontinued.
Metribolone is an AAS, or an agonist of the AR, with both anabolic and androgenic activity. It is one of the most potent AAS to have ever been synthesized, with 120 to 300 times the oral anabolic potency and 60 to 70 times the androgenic potency of the reference AAS methyltestosterone in castrated male rats, although the same level of potency was not subsequently seen in later studies in humans. In addition to the AR, metribolone has high affinity for the progesterone receptor (PR), and binds to the glucocorticoid receptor (GR) as well. Metribolone has a high potential for hepatotoxicity, similarly to other 17α-alkylated AAS. However, the hepatotoxic potential of metribolone appears to be exceptionally high, likely in relation to its very high potency and metabolic stability; in a study of treatment with the drug for advanced breast cancer, severe hepatic dysfunction was observed at very low dosages.
Metribolone was identified in 2010 as a potent inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD) 1 and 2 (IC50 = 0.02 and 0.16 μM, respectively). On the basis of this finding, it has been said that metribolone should be used very cautiously taking into account 3β-HSD inhibition in scientific research to avoid erroneous interpretation.
Metribolone, also known as 17α-methyltrenbolone, as well as 17α-methyl-δ9,11-19-nortestosterone or 17α-methylestra-4,9,11-triene-17β-ol-3-one, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone (19-nortestosterone). It is the C17α methylated derivative of trenbolone (δ9,11-19-nortestosterone) and the C9- and C11-dehydrogenated (δ9,11) analogue of normethandrone (17α-methyl-19-nortestosterone). Other close relatives and derivatives of metribolone include mibolerone (7α,17α-dimethyl-19-nortestosterone) and dimethyltrienolone (RU-2420; 7α,17α-dimethyl-δ9,11-19-nortestosterone). In addition to AAS, trimethyltrienolone (R2956; 2α,2β,17α-trimethyl-δ9,11-19-nortestosterone), a highly potent antiandrogen, has been derived from metribolone.
Metribolone was first described in the literature in 1965. It was studied clinically in the late 1960s and early 1970s, most notably in the treatment of advanced breast cancer. The drug was found to be effective and showed weak androgenicity, but also produced severe signs of hepatotoxicity, and was ultimately never marketed. By the mid-1970s, metribolone was becoming an accepted standard as a ligand and agonist of the AR in scientific research. It remains in wide use for this purpose today. Aside from scientific research, metribolone has also been encountered as an AAS in non-medical contexts, for instance in doping in sports and bodybuilding.
Society and culture
Metribolone is the generic name of metribolone and its INN. It is also known by the name methyltrienolone and its developmental code names R1881, R-1881, RU-1881, RU1881, and NSC-92858, and is very commonly referred to by these other names rather than as metribolone in the scientific literature.
Doping in sports
- J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 654–. ISBN 978-1-4757-2085-3.
- William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. pp. 546–. ISBN 978-0-9828280-1-4.
- Brinkmann AO, Kuiper GG, de Boer W, Mulder E, Bolt J, van Steenbrugge GJ, van der Molen HJ (January 1986). "Characterization of androgen receptors after photoaffinity labelling with [3H]methyltrienolone (R1881)". Journal of Steroid Biochemistry. 24 (1): 245–9. PMID 2422446. doi:10.1016/0022-4731(86)90058-0.
- Brueggemeier, Robert W. (2006). "Sex Hormones (Male): Analogs and Antagonists". doi:10.1002/3527600906.mcb.200500066.
- Singh SM, Gauthier S, Labrie F (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Current Medicinal Chemistry. 7 (2): 211–47. PMID 10637363. doi:10.2174/0929867003375371.
- Ho-Kim MA, Tremblay RR, Dubé JY (November 1981). "Binding of methyltrienolone to glucocorticoid receptors in rat muscle cytosol". Endocrinology. 109 (5): 1418–23. PMID 6975208. doi:10.1210/endo-109-5-1418.
- Krüskemper HL, Noell G (July 1966). "Liver toxicity of a new anabolic agent: methyltrienolone (17-alpha-methyl-4,9,11-estratriene-17 beta-ol-3-one)". Steroids. 8 (1): 13–24. PMID 5955468. doi:10.1016/0039-128x(66)90114-0.
- Zheng F (2010). "Methyltrienolone (R1881) is a Potent Inhibitor of 3B-Hydroxysteroid Dehydrogenase (3B-HSD) Activity". Characterization of Enzymes Involved in the Metabolism of Dihydrotestosterone, the Most Potent Natural Androgen (PDF) (thesis). pp. 91–103. Retrieved 19 July 2017.
- V. H. T. James; J. R. Pasqualini (22 October 2013). Proceedings of the Fourth International Congress on Hormonal Steroids: Mexico City, September 1974. Elsevier Science. p. 618. ISBN 978-1-4831-4566-2.
R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 , is a powerful testosterone antagonist with very low androgenic activity.
- A. F. Harms (1 January 1986). Innovative Approaches in Drug Research: Proceedings of the Third Noordwijkerhout Symposium on Medicinal Chemistry, Held in the Netherlands, September 3-6, 1985. Elsevier. ISBN 978-0-444-42606-2.
At this stage, RU 2956 exerts a competitive effect about 4 times less marked than metribolone may be because the steric hindrance of the dimethyl group in position C-2 interferes with H-bond formation between the C-3 oxygen and the receptor protein, i.e., with the recognition step, and consequently, with the association rate.
- "Eleven Greek weightlifters test positive; coach suspended". Associated Press / USATODAY.com. 2008-04-04. Retrieved 2009-06-28.
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