 | |
 | |
| Clinical data | |
|---|---|
| Other names | 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 |
| Routes of administration | By mouth |
| Drug class | Androgen;Anabolic steroid;Progestogen |
| Identifiers | |
| |
| CAS Number |
|
| PubChemCID | |
| IUPHAR/BPS | |
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.190.113 |
| Chemical and physical data | |
| Formula | C19H24O2 |
| Molar mass | 284.399 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
| (verify) | |
Metribolone (developmental codeR1881, also known asmethyltrienolone) is asynthetic andorally activeanabolic–androgenic steroid (AAS) and a17α-alkylatednandrolone (19-nortestosterone)derivative which was never marketed formedical use but has been widely used inscientific research as ahot ligand inandrogen receptor (AR)ligand binding assays (LBAs) and as aphotoaffinity label for the AR.[1][2][3] More precisely, metribolone is the 17α-methylated derivative oftrenbolone. It was investigated briefly for the treatment ofadvanced breast cancer in women in the late 1960s and early 1970s, but was found to produce signs of severehepatotoxicity at very low dosages, and its development was subsequently discontinued.[2][4]
Metribolone was never approved for medical use,[2] a situation unlikely to change given its liver toxicity even at low doses.[2] It was studied for the potential treatment ofadvanced breast cancer in women but development was abandoned.[2][4]
Side effects of metribolone includevirilization andhepatotoxicity among others.[2]
Metribolone is an AAS, or anagonist of the AR, with bothanabolic andandrogenic activity.[2] It is one of the mostpotent 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 AASmethyltestosterone in castrated male rats, although the same level of potency has not been observed in studies in humans.[2][4] In addition to the AR, metribolone has highaffinity for theprogesterone receptor (PR), and binds to theglucocorticoid receptor (GR) as well.[5][6] The drug was also identified in 2007 as a potentantimineralocorticoid, with similar affinity for themineralocorticoid receptor asaldosterone andspironolactone.[7] In addition, metribolone was identified in 2010 as a potent inhibitor of3β-hydroxysteroid dehydrogenase (3β-HSD)1 and2 (IC50 = 0.02 and 0.16 μM, respectively).[8] On the basis of this finding, it has been said that metribolone should be used very cautiously in scientific research, taking into account 3β-HSD inhibition to avoid erroneous interpretation.[8]
Metribolone has a high potential forhepatotoxicity, similarly to other 17α-alkylated AAS.[9] However, the hepatotoxic potential of metribolone appears to be exceptionally high, likely in relation to its very high potency andmetabolic stability; in a study of treatment with the drug foradvanced breast cancer, severe hepatic dysfunction was observed at very low dosages.[4]
| Compound | Chemical name | PRTooltip Progesterone receptor | ARTooltip Androgen receptor | ERTooltip Estrogen receptor | GRTooltip Glucocorticoid receptor | MRTooltip Mineralocorticoid receptor |
|---|---|---|---|---|---|---|
| Testosterone | T | 1.0 | 100 | <0.1 | 0.17 | 0.9 |
| Nandrolone | 19-NT | 20 | 154 | <0.1 | 0.5 | 1.6 |
| Trenbolone | ∆9,11-19-NT | 74 | 197 | <0.1 | 2.9 | 1.33 |
| Trestolone | 7α-Me-19-NT | 50–75 | 100–125 | ? | <1 | ? |
| Normethandrone | 17α-Me-19-NT | 100 | 146 | <0.1 | 1.5 | 0.6 |
| Metribolone | ∆9,11-17α-Me-19-NT | 208 | 204 | <0.1 | 26 | 18 |
| Mibolerone | 7α,17α-DiMe-19-NT | 214 | 108 | <0.1 | 1.4 | 2.1 |
| Dimethyltrienolone | ∆9,11-7α,17α-DiMe-19-NT | 306 | 180 | 0.1 | 22 | 52 |
| Notes: Values are percentages (%). Referenceligands (100%) wereprogesterone for thePRTooltip progesterone receptor,testosterone for theARTooltip androgen receptor,estradiol for theERTooltip estrogen receptor,DEXATooltip dexamethasone for theGRTooltip glucocorticoid receptor, andaldosterone for theMRTooltip mineralocorticoid receptor.Sources:[10][11] | ||||||
| Compound | rAR(%) | hAR(%) | ||||||
|---|---|---|---|---|---|---|---|---|
| Testosterone | 38 | 38 | ||||||
| 5α-Dihydrotestosterone | 77 | 100 | ||||||
| Nandrolone | 75 | 92 | ||||||
| 5α-Dihydronandrolone | 35 | 50 | ||||||
| Ethylestrenol | ND | 2 | ||||||
| Norethandrolone | ND | 22 | ||||||
| 5α-Dihydronorethandrolone | ND | 14 | ||||||
| Metribolone | 100 | 110 | ||||||
| Sources: See template. | ||||||||
Metribolone has very lowaffinity for human serumsex hormone-binding globulin (SHBG), less than 5% of that oftestosterone and less than 1% of that ofdihydrotestosterone (DHT).[12]
Metribolone, also known as 17α-methyltrenbolone, as well as 17α-methyl-δ9,11-19-nortestosterone or 17α-methylestra-4,9,11-trien-17β-ol-3-one, is asyntheticestranesteroid and a17α-alkylatedderivative ofnandrolone (19-nortestosterone).[1][2] It is the C17αmethylated derivative of trenbolone (δ9,11-19-nortestosterone) and the C9- and C11-dehydrogenated (δ9,11)analogue ofnormethandrone (17α-methyl-19-nortestosterone).[1][2] Other close relatives and derivatives of metribolone includemibolerone (7α,17α-dimethyl-19-nortestosterone) anddimethyltrienolone (RU-2420; 7α,17α-dimethyl-δ9,11-19-nortestosterone).[1][2] In addition to AAS,trimethyltrienolone (R2956; 2α,2β,17α-trimethyl-δ9,11-19-nortestosterone), a highly potentantiandrogen, has been derived from metribolone.[13][14]
Metribolone was first described in the literature in 1965.[2] It was studied clinically in the late 1960s and early 1970s, most notably in the treatment of advancedbreast cancer.[2] The drug was found to be effective and showed weak androgenicity, but also produced severe signs of hepatotoxicity, and was ultimately never marketed.[2][4] By the mid-1970s, metribolone was becoming an accepted standard as a ligand and agonist of the AR in scientific research.[2] It remains in wide use for this purpose today.[2] Aside from scientific research, metribolone has also been encountered as an AAS in non-medical contexts, for instance indoping in sports andbodybuilding.[2]
Metribolone is thegeneric name of metribolone and itsINNTooltip International Nonproprietary Name.[1] It is also known by the namemethyltrienolone and its developmental code namesR1881,R-1881,RU-1881, andRU1881, and is very commonly referred to by these other names rather than asmetribolone in the scientific literature.[1]
Prior to the2008 Beijing Olympic Games, 11 members of the Greek national weightlifting team and 4 Greek track and field athletes tested positive for metribolone.[15]
R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 [44], is a powerful testosterone antagonist with very low androgenic activity.
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.
