Nandrolone

Nandrolone

Systematic (IUPAC) name
17β-Hydroxyestra-4-en-3-one
Clinical data
Pregnancy category	Classics (US) X (AUS)
Routes of administration	Intramuscular
Legal status
Legal status	CA: Schedule IV UK: POM (Prescription only) US: Schedule III
Pharmacokinetic data
Bioavailability	2.24% (Oral) 100% (Intramuscular)
Metabolism	Hepatic
Biological half-life	6 days
Excretion	approximate 21 days
Identifiers
CAS Number	434-22-0
ATC code	A14AB01 (WHO) S01XA11
PubChem	CID 9904
IUPHAR/BPS	6949
DrugBank	DB00984
ChemSpider	9520
UNII	6PG9VR430D
ChEBI	CHEBI:7466
ChEMBL	CHEMBL757
Chemical data
Formula	C18H26O2
Molar mass	274.40
SMILES O=C4\C=C2/[C@@H]([C@H]1CC[C@@]3([C@@H](O)CC[C@H]3[C@@H]1CC2)C)CC4
InChI InChI=1S/C18H26O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h10,13-17,20H,2-9H2,1H3/t13-,14+,15+,16-,17-,18-/m0/s1 Key:NPAGDVCDWIYMMC-IZPLOLCNSA-N
(what is this?)  (verify)

Nandrolone (/ˈnændrəloʊn/,^[1] 19-nortestosterone) is an anabolic steroid. Nandrolone is most commonly sold commercially as its decanoate ester (Deca-Durabolin, eubolin, retabolil) and less commonly as a phenylpropionate ester (Durabolin, fenobolin). Nandrolone decanoate is used in the treatment of osteoporosis in postmenopausal women (though now not recommended) at a dose of 50 mg every three weeks. It is also used for some aplastic anemias.

Metabolism

The positive effects of the drug include muscle growth, appetite stimulation and increased red blood cell production and bone density. Clinical studies have shown it to be effective in treating anaemia, osteoporosis and some forms of neoplasia including breast cancer, and also acts as a progestin-based contraceptive. For these reasons, in the United States nandrolone received FDA approval in 1983.

Because nandrolone is not broken down into DHT, the deleterious effects common to most anabolic steroids on the scalp, skin, and prostate are lessened to a degree; but is rather broken down to the much weaker androgen dihydronandrolone. The lack of alkylation on the 17α-carbon drastically reduces the drug's liver toxicity. Estrogenic effects resulting from reaction with aromatase are also reduced due to lessened enzyme interaction,^[2] but effects such as gynaecomastia and reduced libido still occur in larger doses because of other mechanisms. Other side-effects of abuse can include erectile dysfunction and cardiovascular damage, as well as several ailments resulting from the drug's effect of lowering levels of luteinizing hormone through negative feedback. Erectile dysfunction is attributed to the weaker action of dihydronandrolone in the penis since dihydrotestosterone is a known sexual modulator.

Detection method

Nandrolone use is directly detectable in hair or indirectly detectable in urine by testing for the presence of 19-norandrosterone, a metabolite. The International Olympic Committee has set a limit of 2.0 μg/L of 19-norandrosterone in urine as the upper limit,^[3] beyond which an athlete is suspected of doping. In the largest nandrolone study performed on 621 athletes at the 1998 Nagano Olympic Games, no athlete tested over 0.4 μg/L. 19-Norandrosterone was identified as a trace contaminant in commercial preparations of androstenedione, which until 2004 was available without a prescription as a dietary supplement in the U.S.^[4][5][6][7]

A number of nandrolone cases in athletics occurred in 1999, which included high profile athletes such as Merlene Ottey, Dieter Baumann and Linford Christie.^[8] However, the following year the detection method for nandrolone at the time was proved to be faulty. Mark Richardson, a British Olympic relay runner who tested positive for the substance, gave a significant amount of urine samples in a controlled environment and delivered a positive test for the drug, demonstrating that false positives could occur, which led to an overhaul of his competitive ban.^[9]

Heavy consumption of the essential amino acid lysine (as indicated in the treatment of cold sores) has allegedly shown false positives in some and was cited by American shotputter C. J. Hunter as the reason for his positive test, though in 2004 he admitted to a federal grand jury that he had injected nandrolone.^[10] A possible cause of incorrect urine test results is the presence of metabolites from other anabolic steroids, though modern urinalysis can usually determine the exact steroid used by analyzing the ratio of the two remaining nandrolone metabolites. As a result of the numerous overturned verdicts, the testing procedure was reviewed by UK Sport. On October 5, 2007, five-time gold medalist for track and field Marion Jones admitted to use of the drug, and was sentenced to six months in jail for lying to a federal grand jury in 2000.^[11]

QV Nandrolone Deca, a form of nandrolone used by athletes.

Mass spectrometry is also used to detect small samples of nandrolone in urine samples, as it has a unique molar mass.

Publicized cases

• In November 1994, South Africa's Jamie Bloem was the first rugby league footballer to test positive for nandrolone. He was banned for two years.^[12]
• Spain's Pep Guardiola tested positive for nandrolone while playing for Brescia.^[13]
• Petr Korda tested positive for nandrolone after his 1998 Wimbledon quarter final match against Tim Henman. Korda was banned from tennis for one year from September 1999.^[14]
• Roger Clemens, who was a member of the 2000 World Series winning New York Yankees, was reported to have been injected with nandrolone (Deca-Durabolin) by major league strength coach Brian McNamee during the 2000 baseball season.^[15]
• ATP Tennis Pro Guillermo Coria tested positive for nandrolone in 2001, causing him to be suspended for 6 months from the sport^[16]
• UFC Hall of Famer Royce Gracie tested positive for nandrolone after defeating his longtime rival Kazushi Sakuraba at K-1 Dynamite!! USA in 2007. He was fined $2,500 and suspended for the remainder of his license.^[17]
• Shoaib Akhtar, a Pakistani cricketer, was given a two-year ban in 2006 for testing positive for nandrolone. Shoaib was sent back to Pakistan and missed out competing for the Champions Trophy. The verdict, however, was overturned by a three-man tribunal a month later.^[18]
• Sean Sherk, former UFC Lightweight Champion, tested positive for nandrolone following his title defence to Hermes Franca at UFC 73 Interestingly enough, Franca also tested positive for Nandrolone. Sherk passed a lie detector test claiming that he did not knowingly take steroids but the UFC still stripped Sherk of the lightweight title.^[19]
• Linford Christie, a British sprinter and 1992 Olympic gold medalist, tested positive for nandrolone in 1999.^[20]
• Former Maryland Terrapin and NBA player Juan Dixon tested positive for use of this drug in 2009, which earned him a suspension by the International Basketball Federation.^[21]
• In September 2010, Baltimore Orioles minor league shortstop Alfredo Zambrano received a 50-game suspension for the 2011 season as a result of testing positive for metabolites of nandrolone.^[22]
• Indian athlete Rani Yadav and Sri Lankan boxer Manju Wanniarachchi tested positive for nandrolone at the 2010 Commonwealth Games.^[23]
• British tennis player Greg Rusedski tested positive for nandrolone in January 2004,^[24] but was cleared of the charges in a hearing on 10 March 2004.^[25]
• In August 2014, New York Mets minor league right handed pitcher Derrick Bernard received a 62-game suspension as a result of testing positive for metabolites of nandrolone.^[26]

Synthesis

The elaboration of a method for the reduction of aromatic rings to the corresponding dihydrobenzenes under controlled conditions by A. J. Birch opened a convenient route to compounds related to the putative norprogesterone.

19-Nortestosterone synthesis:^[27] alternative:^[28][29]

This reaction, now known as the Birch reduction,^[30] is typified by the treatment of the monomethyl ether of estradiol (1) with a solution of lithium metal in liquid ammonia in the presence of alcohol as a proton source. Initial reaction constituents of 1,4-dimetalation of the most electron deficient positions of the aromatic ring–in the case of an estrogen, the 1 and 4-positions. Rxn of the intermediate with the proton source leads to a dihydrobenzene; a special virtue of this sequence in steroids is the fact that the double bind at 2 is in effect becomes an enol ether moiety. Treatment of this product (2) with weak acid, oxalic acid for eg, leads to the hydrolysis of the enol ether, producing β,γ-unconjugated ketone 3. Hydrolysis under more sternuous conditions (mineral acids) results in migration/conjugation of the olefin to yield nandrolone (4).

Esters

• Treatment of 4 with decanoic anhydride and pyridine affords nandrolone decanoate.^[31]
• Acylation of 4 with phenylpropionyl chloride yields nandrolone phenpropionate.^[32]

See also

• 19-Norprogesterone

References

1. http://dictionary.cambridge.org/dictionary/british/nandrolone
2. Brueggemeier RW (September 16, 2006). "Sex Hormones (Male): Analogs and Antagonists". In Meyers RA. Encyclopedia of Molecular Cell Biology and Molecular Medicine. Encyclopedia of Molecular Cell Biology and Molecular Medicine (abstract). John Wiley & Sons. doi:10.1002/3527600906.mcb.200500066. ISBN 3527600906. Retrieved March 2, 2013.
3. "Clarification about Nandrolone Testing". World Anti-Doping Agency. 2005-05-30. Retrieved 2012-01-31.
4. Bresson M, Cirimele V, Villain M, Kintz P (May 2006). "Doping control for metandienone using hair analyzed by gas chromatography-tandem mass spectrometry". J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 836 (1–2): 124–8. doi:10.1016/j.jchromb.2006.03.040. PMID 16597518.
5. Ueki M, Ikekita A, Takao Y (2000). "[Nandrolone metabolite in urine of Nagano Olympic athlete]". Jap. J. For. Tox. (in Japanese) 18: 198–199.
6. Catlin DH, Leder BZ, Ahrens B, Starcevic B, Hatton CK, Green GA, Finkelstein JS (2000). "Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite". JAMA 284 (20): 2618–21. doi:10.1001/jama.284.20.2618. PMID 11086369.
7. Baselt RC (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1078–1080. ISBN 0-9626523-7-7.
8. Baron, Peter (2000-09-19). The Drugs Issue: Baumann to fight all the way. The Daily Telegraph. Retrieved on 2010-11-13.
9. Richardson M (2004-02-19). "Athletics: Mark Richardson explains how he felt at his disciplinary hearing". Athletics (London: The Guardian). Retrieved 2010-11-13. It was as daunting a line-up as I had ever faced on athletics tracks
10. "Track Star Marion Jones to Admit Steroid Use". National Public Radio. 2007-10-05. Retrieved 2009-11-09.
11. UK Sport Anti-doping Direcorate (January 2000). Nandrolone Review (PDF) (Report). UK Sport. Archived from the original (PDF) on 2005-04-02. Retrieved 2013-02-02.
12. "Disgraced Hudson faces sack from Bulls". Daily Mail (London). March 10, 2005.
13. "Guardiola fails second test". BBC News. November 28, 2001.
14. "Korda failed Wimbledon drugs test". BBC. December 23, 1998.
15. All-Star Roster Shows Up on Mitchell Report washingtonpost.com, 12-13-2007
16. "BBC Sport".
17. "Royce Gracie Suspended, Fined For Steroids | TheSweetScience.com Boxing". Thesweetscience.com. Retrieved November 9, 2009.
18. "Cricinfo - A tale of intrigue, injuries and incidents". Content-ind.cricinfo.com. January 1, 1970. Retrieved November 9, 2009.
19. "Sean Sherk". Cage Potato. January 1, 1970. Retrieved September 12, 2010.
20. "news.bbc.co.uk/2/hi/sport/411951.stm". BBC News. August 4, 1999. Retrieved November 9, 2009.
21. "Former NBA player banned after steroid test". USA Today. February 13, 2010.
22. "Three Minor League players suspended". MLB.com. September 30, 2010.
23. Indian athlete Rani Yadav fails dope test at Commonwealth Games, The Times of India, October 13, 2010.
24. "news.bbc.co.uk/sport1/hi/tennis/3381111.stm". BBC News. January 9, 2004. Retrieved July 2, 2011.
25. "http://news.bbc.co.uk/sport1/hi/tennis/3547917.stm". BBC News. March 10, 2004. Retrieved July 2, 2011. External link in |title= (help)
26. "Minor leaguer suspended". August 13, 2014.
27. Wilds, A. L.; Nelson, Norman A. (1953). "The Facile Synthesis of 19-Nortestosterone and 19-Norandrostenedione from Estrone". Journal of the American Chemical Society 75 (21): 5366. doi:10.1021/ja01117a065.
28. Ueberwasser, H.; Heusler, K.; Kalvoda, J.; Meystre, Ch.; Wieland, P.; Anner, G.; Wettstein, A. (1963). "19-Norsteroide II. Ein einfaches Herstellungsverfahren für 19-Norandrostan-Derivate. Über Steroide, 193. Mitteilung". Helvetica Chimica Acta 46: 344. doi:10.1002/hlca.19630460135.
29. Shimizu, Isao; Naito, Yoichiro; Tsuji, Jiro (1980). "Synthesis of optically active (+)-19-nortestosterone by asymmetric bis-annulation reaction". Tetrahedron Letters 21 (5): 487. doi:10.1016/S0040-4039(00)71440-7.
30. Birch, Arthur J. (1950). "The reduction of organic compounds by metal-ammonia solutions". Quarterly Reviews, Chemical Society 4: 69. doi:10.1039/QR9500400069.
31. DeWytt, E. D.; Overbeek, O.; Overbeek, G. A.; U.S. Patent 2,998,423 (1961 to Organon).
32. CH 206119  (1939 to Gesellschaft für Chemische Industrie Basel).