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

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 Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

(19-nortestosterone)

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

which was never marketed for medical use but has been widely used in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

as a hot ligand in

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 assay 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-re ...

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

trenbolone Trenbolone is an androgen and anabolic steroid (AAS) of the nandrolone group which itself was never marketed. Trenbolone ester prodrugs, including trenbolone acetate (brand names Finajet, Finaplix, others) and trenbolone hexahydrobenzylcarbonate ...

. It was investigated briefly for the treatment of

advanced breast cancer Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary l ...

in women in the late 1960s and early 1970s, but was found to produce signs of severe

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

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

in women but development was abandoned.

Side effects

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of metribolone include

virilization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...

and

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 Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-do ...

and

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...

ic 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 The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates ...

(GR) as well. The drug was also identified in 2007 as a potent

antimineralocorticoid An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often u ...

, with similar affinity for the

mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

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 Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure ...

. 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

, 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

, severe hepatic dysfunction was observed at very low dosages.

Pharmacokinetics

Metribolone has very low

for human serum

sex hormone-binding globulin Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen-bi ...

(SHBG), less than 5% of that of

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

and less than 1% of that of

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...

(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

(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 Mibolerone, also known as dimethylnortestosterone (DMNT) and sold under the brand names Cheque Drops and Matenon, is a synthetic compound, synthetic, oral administration, orally active, and extremely potency (pharmacology), potent anabolic–andr ...

(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 Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an antiandrogen medication which was never introduced for medical use but has been used in scientific research. Side effects Due to its close relation to m ...

(R2956; 2α,2β,17α-trimethyl-δ^9,11-19-nortestosterone), a highly potent

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...

, 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 Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

. 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 Bodybuilding is the use of progressive resistance exercise to control and develop one's muscles (muscle building) by muscle hypertrophy for aesthetic purposes. It is distinct from similar activities such as powerlifting because it focuses ...

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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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Glucocorticoid receptor modulators {{Mineralocorticoid receptor modulators {{Progesterone receptor modulators 3β-Hydroxysteroid dehydrogenase inhibitors Tertiary alcohols Androgens and anabolic steroids Antimineralocorticoids Estranes Glucocorticoids Hepatotoxins Enones Progestogens World Anti-Doping Agency prohibited substances Abandoned drugs