Metandienone

Metandienone
Clinical data
Trade names Averbol, Dianabol, Danabol, Metanabol, Naposim, Vetanabol
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration		 Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 4.5–6 hours
Excretion Renal
Identifiers
Synonyms Methandienone; Methandrostenolone; Methandrolone; Dehydromethyltestosterone; Methylboldenone; NSC-51180; NSC-42722; 17α-Methyl-δ1-testosterone; 17α-Methylandrost-1,4-dien-17β-ol-3-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
ECHA InfoCard 100.000.716
Chemical and physical data
Formula C20H28O2
Molar mass 300.441 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

Metandienone (INN) (brand names Averbol, Dianabol, Danabol, Metanabol, Naposim, Vetanabol), or methandienone (BAN), also commonly known as methandrostenolone, is a synthetic, orally active anabolic-androgenic steroid (AAS) and a 17α-methylated derivative of testosterone which was formerly used medically but has since been discontinued in most countries.[1][2][3] It has also seen non-medical use as a performance-enhancing drug.[3]

Metandienone was originally developed in 1957 by CIBA and marketed in Germany and the United States.[1][4][5][6] As the CIBA product Dianabol, metandienone quickly became the first widely used AAS among professional and amateur athletes, and remains the most common orally active AAS for non-medical use.[7][5][8][9]

It is currently a controlled substance in the U.S.[10] and U.K.[11] and remains popular among bodybuilders. Metandienone is readily available without a prescription in certain countries such as Mexico (under the brand name Reforvit-b), and is also manufactured in some Asian countries.[12]

Medical uses

Metandienone was formerly approved and marketed for the treatment of hypogonadism, but has since been discontinued and withdrawn in most countries, including in the United States.[13][2][12]

Non-medical use

Metandienone confiscated by the DEA in 2008.

Bodybuilding

It is used by bodybuilders and metandienone continues to be used illegally to this day, typically being combined (stacked) with injectable compounds, such as testosterone propionate, enanthate, cypionate as well as other injectable drugs like trenbolone acetate.

Several successful athletes and professional bodybuilders have admitted long-term metandienone use before the drug was banned, including Arnold Schwarzenegger.[14][15] Other steroids stacked with metandienone are primarily, if not always, injectable compounds such as testosterone, trenbolone and nandrolone. Large doses and long-term use of metandienone have been associated with eccentric left ventricular hypertrophy which presents substantially increased risks of cardiomyopathy if and when the hypertrophy atrophies. Athleticism is typically associated with left-ventricular hypertrophy; however, natural athleticism generally presents concentric left ventricular growth which is not linked to an increased risk of cardiomyopathy.

Side effects

Pharmacology

Metandienone binds to and activates the androgen receptor (AR) in order to exert its effects.[16] These include dramatic increases in protein synthesis, glycogenolysis, and muscle strength over a short space of time. Side effects such as gynecomastia, high blood pressure, acne and male pattern baldness may begin to occur. The drug causes severe masculinizing effects in women even at low doses. In addition, it is metabolized into methylestradiol by aromatase.[3] This means that without the administration of aromatase inhibitors such as anastrozole or aminoglutethimide, estrogenic effects like gynecomastia (breast development) may appear over time in men. Many users combat the estrogenic side effects with anastrozole, tamoxifen or clomifene. In addition, as with other 17α-alkylated steroids, the use of metandienone over extended periods of time can result in liver damage without appropriate precautions.

The 17α-methylation of the steroid does allow it to pass through the liver with only a small portion of it broken down (hence causing the aforementioned damage to the liver) allowing it to be effective when taken orally. It also has the effect of decreasing the steroid's affinity for sex hormone-binding globulin, a protein that deactivates steroid molecules and prevents them from further reactions with the body. As a result, metandienone is significantly more active than an equivalent quantity of testosterone, resulting in rapid growth of muscle tissue. However, the concomitant elevation in estrogen levels – a result of the aromatization of metandienone – results in significant water retention. This gives the appearance of bad gains in mass and strength, which proves to be temporary once the steroid is discontinued and water weight drops. Because of this, it is often used by bodybuilders at the start of a "steroid cycle", to facilitate rapid strength increases and the appearance of great size, while compounds such as testosterone cypionate or testosterone enanthate with long acting esters build up in the body to an appreciable amount capable of supporting anabolic function on their own.

Chemistry

Metandienone, also known structurally as 17α-methyl-δ1-testosterone or as 17α-methylandrost-1,4-dien-17β-ol-3-one, is a 17α-alkylated androstane steroid and a derivative of testosterone.[1] It is a modification of testosterone with a methyl group at the C17α position and an additional double bond between the C1 and C2 positions.[1] The drug is also the 17α-methylated derivative of boldenone (δ1-testosterone) and the δ1 analogue of methyltestosterone (17α-methyltestosterone).[1]

Detection in body fluids

Metandienone is subject to extensive hepatic biotransformation by a variety of enzymatic pathways. The primary urinary metabolites are detectable for up to 3 days, and a recently discovered hydroxymethyl metabolite is found in urine for up to 19 days after a single 5 mg oral dose.[17] Several of the metabolites are unique to metandienone. Methods for detection in urine specimens usually involve gas chromatography-mass spectrometry.[18][19]

History

Metandienone was first synthesized in 1956 by researchers at the CIBA laboratories in Basel, Switzerland. CIBA filed for a US patent in 1957,[20] and began marketing the compound as Dianabol in 1958.[21]

Beginning soon afterwards in 1959, CIBA collaborated with John Bosley Ziegler (a physician specializing in physical rehabilitation and an early pioneer of pharmaceutical performance enhancement) to test the effects of Dianabol on professional weightlifters. Ziegler had a close relationship with Bob Hoffman, owner of York Barbell Company and coach of the US Olympic weightlifting team,[22][23] granting him access to subjects in peak performance condition.[24][21][6]

The first tentative experiments were disappointing. For example, AAU Mr. America winner Jim Park reported that "its only effect was to give him an instant erection upon seeing any female." However, Ziegler believed that Dianabol had significant potential as an anabolic. During the lead-up to the 1960 Olympics, he proposed to Hoffman that it be administered to top members of the American Olympic team. Hoffman, however, was cautious and later remarked it was "too close to give to the men who will represent the USA". According to Grimek, "apparently, he doesn’t think it will do that much good, and may even have detrimental effects, ... He appears doubtful." [6]

Instead, Dianabol was given to various lower level lifters to investigate its effectiveness and safety. Among the first subjects were John Grimek, Bill March, Charles Vinci, and Louis Riecke, as well as Ziegler and Hoffman themselves.[6] Hoffman later commented on the startling effects of the new drug, saying that "in five days I could curl and press more and I gained weight", and that "when I went to a weight lifting contest, or when I had my coat off anywhere, people would say, ‘Where did you get all those muscles?’”.[6] Riecke gained muscle mass and strength rapidly, and reported a "constant feeling of euphoria and energy." His results drew enormous interest among other elite weightlifters, and rumors spread that Ziegler had made a major breakthrough in his research. He attempted to deflect their curiosity with hints of new isometric and hypnotic techniques.[6]

Over the course of the next 2 years, Ziegler's work with Riecke further explored the new drug's physical and psychological effects. Riecke's performance and mood consistently improved while taking Dianabol, and dramatically declined when he did not take it. John Fair also suggests that Riecke was among the first cases of steroid dependency, at one point "mentioning the pills four times in [one] letter, twice being reminders for Ziegler to send more."[6]

From 1962 onward, it became increasingly difficult for Ziegler and others to keep their results secret, and word of Dianabol's spectacular performance-enhancing effects gradually spread among competitors in other sports where strength or mass were critical factors in an athlete's success. American football players and coaches were particularly interested in the new "anabolic".[24] Early adopters included players for Oklahoma University and San Diego Chargers head coach Sid Gillman, who administered Dianabol to his team starting in 1963.[21][7][25]

After the Kefauver Harris Amendment was passed in 1962, the US FDA began the DESI review process to ensure the safety and efficacy of drugs approved under the more lenient pre-1962 standards, including Dianabol.[26] In 1965, the FDA pressured CIBA to further document its legitimate medical uses, and re-approved the drug for treating post-menopausal osteoporosis and pituitary-deficient dwarfism.[27] After CIBA's patent exclusivity period lapsed, other manufacturers began to market generic metandienone in the US.

Following further FDA pressure, CIBA withdrew Dianabol in 1983. Generic production shut down two years later, when the FDA revoked metandienone's approval entirely in 1985.[27][28] Non-medical use was outlawed in the US under the Anabolic Steroids Control Act of 1990.[29]

Society and culture

Metandienone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act.[30]

See also

Footnotes

  1. 1 2 3 4 5 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 781–. ISBN 978-1-4757-2085-3.
  2. 1 2 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. p. 660. ISBN 978-3-88763-075-1.
  3. 1 2 3 William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. pp. 444,533. ISBN 978-0-9828280-1-4.
  4. ↑ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 660–. ISBN 978-3-88763-075-1.
  5. 1 2 Yesalis CE, Anderson WA, Buckley WE, Wright JE (1990). "Incidence of the nonmedical use of anabolic-androgenic steroids" (PDF). NIDA Res. Monogr. 102: 97–112. PMID 2079979.
  6. 1 2 3 4 5 6 7 Fair JD (1993). "Isometrics or Steroids? Exploring New Frontiers Of Strength in the Early 1960s" (PDF). Journal of Sport History. 20 (1): 1–24. Archived from the original (PDF) on 2008-05-28.
  7. 1 2 Yesalis, Charles; Bahrke, Michael (2002). "History of Doping in Sport" (PDF). International Sports Studies. 24: 42–76.
  8. ↑ Lin, Geraline C.; Erinoff, Lynda (1996-07-01). Anabolic Steroid Abuse. DIANE Publishing. ISBN 9780788129698.
  9. ↑ Helms, Eric (August 2014). "What can be achieved as a natural bodybuilder?" (PDF). Alan Aragon's Research Review. Alan Aragon.
  10. ↑ Drug Enforcement Administration. "Controlled Substances, Alphabetical Order" (PDF).
  11. ↑ "List of most commonly encountered drugs currently controlled under the misuse of drugs legislation - GOV.UK". www.gov.uk. Retrieved 2017-01-14.
  12. 1 2 https://www.drugs.com/international/metandienone.html
  13. ↑ Donald G. Barceloux (3 February 2012). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons. pp. 275–. ISBN 978-1-118-10605-1.
  14. ↑ "Interview with Sergio Oliva". Retrieved 2010-10-18.
  15. ↑ "Arnold & Steroids: Truth Revealed". Retrieved 10 April 2015.
  16. ↑ Roselli CE (May 1998). "The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area". Brain Res. 792 (2): 271–6. PMID 9593936. doi:10.1016/S0006-8993(98)00148-6.
  17. ↑ Schänzer W, Geyer H, Fusshöller G, Halatcheva N, Kohler M, Parr MK, Guddat S, Thomas A, Thevis M. Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urine. Rapid Commun. Mass Spectrom. 20: 2252-8, 2006.
  18. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 952-954.
  19. ↑ Fragkaki AG, Angelis YS, Tsantili-Kakoulidou A, Koupparis M, Georgakopoulos C. Schemes of metabolic patterns of anabolic androgenic steroids for the estimation of metabolites of designer steroids in human urine. J. Steroid Biochem. Mol. Biol. 115: 44-61, 2009.
  20. ↑ , Albert, Wettstein; Hunger Alfred & Meystre Charles, "Process for the manufacture of steroid dehydrogenation products"
  21. 1 2 3 "Dianabol, the first widely used steroid, turns 50". NY Daily News. Retrieved 2017-01-14.
  22. ↑ "The Ultimate Strength Exercise 1, Bill Starr" (PDF). Retrieved 2012-02-13.
  23. ↑ "The Ultimate Strength Exercise 2, Bill Starr" (PDF). Retrieved 2012-02-13.
  24. 1 2 Peters, Justin (2005-02-18). "The Man Behind the Juice". Slate. ISSN 1091-2339. Retrieved 2017-01-14.
  25. ↑ "OTL: Football's first steroids team? The '63 Chargers". ESPN.com. 2009-02-01. Retrieved 2017-01-14.
  26. ↑ Fourcroy, Jean. "Designer steroids: past, present and future". Current Opinion in Endocrinology and Diabetes. 13 (3): 306–309. doi:10.1097/01.med.0000224812.46942.c3.
  27. 1 2 Llewellyn, William (2011-01-01). Anabolics. Molecular Nutrition Llc. ISBN 9780982828014.
  28. ↑ Roach, Randy (2017-01-14). Muscle, Smoke and Mirrors. AuthorHouse. ISBN 9781467038409.
  29. ↑ "Rules - 2005 - Implementation of the Anabolic Steroid Control Act of 2004". www.deadiversion.usdoj.gov. Retrieved 2017-01-14.
  30. ↑ Steven B. Karch, MD, FFFLM (21 December 2006). Drug Abuse Handbook, Second Edition. CRC Press. pp. 30–. ISBN 978-1-4200-0346-8.

Other references

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