Metribolone (code name R1881), also known as methyltrienolone, is a synthetic and orally active anabolic androgenic steroid (AAS) and a derivative of 17α-alkylated nandrolone (19-nortestosterone) that has never been marketed for medical use but is widely used in research. as a hot ligand in androgen receptor (AR) ligand binding assays (LBA) and as a photoaffinity marker for AR. More specifically, metribolone is a 17α-methylated derivative of trenbolone. It was briefly studied in the late 1960s and early 1970s for the treatment of advanced breast cancer in women, but was found to show signs of severe hepatotoxicity at very low doses and was later discontinued.
Metribolone was first described in the literature in 1965. It was studied clinically in the late 1960s and early 1970s, particularly in the treatment of advanced breast cancer. The drug proved to be effective and showed little androgenicity, but also caused severe signs of hepatotoxicity and was never marketed in the end. By the mid-1970s, metribolone had become an accepted standard as an AR ligand and agonist in scientific research. It is still widely used for this purpose. In addition to scientific research, metribolone can also be found as an AAS for non-medical purposes such as doping in sports and bodybuilding.
Metribolone is an AAS or AR agonist with anabolic and androgenic activity. It is one of the most potent AASs ever synthesized, with 120-300 times greater anabolic activity when taken orally and 60-70 times the androgenic activity of reference AAS methyltestosterone in castrated male rats, although the level of activity remains the same. has not been seen in human studies. In addition to AR, metribolone has a high affinity for the progesterone receptor (PR) and also binds to the glucocorticoid receptor (GR). In 2007, the drug was also identified as an effective antimineralocorticoid with similar mineralocorticoid receptor affinity for aldosterone and spironolactone. In addition, metribolone was identified in 2010 as a potent inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD) 1 and 2 (IC50 = 0.02 and 0.16 M, respectively). Based on this finding, it has been suggested that metribolone should be used with extreme caution in studies of 3β-HSD inhibition to avoid misinterpretation.
Metribolone has a high potential for hepatotoxicity, as do other 17α-alkylated AAS. However, the hepatotoxic potential of metribolone was found to be exceptionally high, probably due to its very high potency and metabolic stability; In advanced drug therapy for breast cancer, severe hepatic impairment has been observed at very low doses.