Metribolone (developmental code R1881, also known as methyltrienolone) is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

and

orally active Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...

anabolic–androgenic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...

(AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for

medical use Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practice ...

but has been widely used in scientific research as a

hot ligand A ligand binding assay (LBA) is an assay, or an analytic procedure, which relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. A detection method is used to determine the presence and extent of the ligand-rece ...

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

(AR) ligand binding assays (LBAs) and as a photoaffinity label for the AR. More precisely, metribolone is the 17α-methylated derivative of trenbolone. 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.

Medical uses

Metribolone was never approved for medical use, a situation unlikely to change given its liver toxicity even at low doses. It was studied for the potential treatment of advanced breast cancer in women but development was abandoned.

Side effects

Side effects of metribolone include virilization and hepatotoxicity among others.

Pharmacology

Pharmacodynamics

Metribolone is an AAS, or an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

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 Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low ...

in castrated male rats, although the same level of potency has not been observed in studies in humans. In addition to the AR, metribolone has high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

for the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

(PR), and binds to the glucocorticoid receptor (GR) as well. The drug was also identified in 2007 as a potent antimineralocorticoid, with similar affinity for the mineralocorticoid receptor as

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

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 μM, respectively). 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. 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 Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

; in a study of treatment with the drug for advanced breast cancer, severe hepatic dysfunction was observed at very low dosages.

Pharmacokinetics

Metribolone has very low

for human serum sex hormone-binding globulin (SHBG), less than 5% of that of testosterone and less than 1% of that of dihydrotestosterone (DHT).

Chemistry

Metribolone, also known as 17α-methyltrenbolone, as well as 17α-methyl-δ^9,11-19-nortestosterone or 17α-methylestra-4,9,11-trien-17β-ol-3-one, is a

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and a 17α-alkylated derivative of nandrolone (19-nortestosterone). It is the C17α

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

ated derivative of trenbolone (δ^9,11-19-nortestosterone) and the C9- and C11-

dehydrogenated In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

(δ^9,11) analogue of

normethandrone Normethandrone, also known as methylestrenolone or methylnortestosterone and sold under the brand name Metalutin among others, is a progestin and androgen/anabolic steroid (AAS) medication which is used in combination with an estrogen in the tre ...

(17α-methyl-19-nortestosterone). Other close relatives and derivatives of metribolone include mibolerone (7α,17α-dimethyl-19-nortestosterone) and

dimethyltrienolone Dimethyltrienolone (developmental code name RU-2420) is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and 17α-alkylated 19-nortestosterone (nandrolone) derivative which was never marketed for medical ...

(RU-2420; 7α,17α-dimethyl-δ^9,11-19-nortestosterone). In addition to AAS, trimethyltrienolone (R2956; 2α,2β,17α-trimethyl-δ^9,11-19-nortestosterone), a highly potent antiandrogen, has been derived from metribolone.

History

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 sport In competitive sports, doping is the use of banned athletic performance-enhancing drugs by athletic competitors as a way of cheating in sports. The term ''doping'' is widely used by organizations that regulate sporting competitions. The use of ...

s and bodybuilding.

Society and culture

Generic names

''Metribolone'' is the generic name of metribolone and its . It is also known by the name ''methyltrienolone'' and its developmental code names ''R1881'', ''R-1881'', ''RU-1881'', and ''RU1881'', and is very commonly referred to by these other names rather than as ''metribolone'' in the scientific literature.

Doping in sports

Prior to the

2008 Beijing Olympic Games The 2008 Summer Olympics (), officially the Games of the XXIX Olympiad () and also known as Beijing 2008 (), were an international multisport event held from 8 to 24 August 2008, in Beijing, China. A total of 10,942 athletes from 204 Nati ...

, 11 members of the Greek national weightlifting team and 4 Greek track and field athletes tested positive for metribolone.

References

External links

*
Methyltrienolone - William Llewellyn's Anabolic.org
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