Nandrolone

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Nandrolone
Nandrolone.svg
Systematic (IUPAC) name
17β-Hydroxyestra-4-en-3-one
Clinical data
Pronunciation /ˈnændrəln/[1]
Pregnancy
category
Routes of
administration
Intramuscular
Legal status
Legal status
Pharmacokinetic data
Bioavailability 2.24% (Oral)
100% (Intramuscular)
Metabolism Hepatic
Biological half-life 6 days
Excretion ~21 days
Identifiers
CAS Number 434-22-0 YesY
ATC code A14AB01 (WHO) S01XA11 (WHO)
PubChem CID 9904
IUPHAR/BPS 6949
DrugBank DB00984 N
ChemSpider 9520 YesY
UNII 6PG9VR430D YesY
ChEBI CHEBI:7466 YesY
ChEMBL CHEMBL757 YesY
Synonyms Nortestosterone, 19-nortestosterone, 10-nortestosterone, norandrostenolone, nortestosterone, nortestrionate, nortestonate, oestrenolone, estrenolone, SG-4341[2][3]
Chemical data
Formula C18H26O2
Molar mass 274.40
 NYesY (what is this?)  (verify)

Nandrolone (INN, BAN), also known as 19-nortestosterone or 19-norandrostenolone, is a semisynthetic anabolic-androgenic steroid (AAS) derived from testosterone.[2][3] The drug itself is inactive orally due to its lack of a 17α-alkyl group (which renders it vulnerable to extensive first-pass metabolism) and is not actually employed in medicine.[3][4] Instead, nandrolone is used in the form of a variety of long-acting prodrug esters (see nandrolone ester) for intramuscular injection, the most common of which are nandrolone decanoate (Deca-Durabolin, Eubolin, Retabolil) and, to a lesser extent, nandrolone phenylpropionate (Durabolin, Fenobolin).[3][4]

Pharmacology[edit]

The positive effects of the drug include muscle growth, appetite stimulation and increased red blood cell production,[medical citation needed] and bone density.[5] Clinical studies have shown it to be effective in treating anemia, osteoporosis and some forms of neoplasia including breast cancer, and also acts as a progestin-based contraceptive.

Unlike testosterone and certain other anabolic steroids, nandrolone is not potentiated in androgenic tissues like the scalp, skin, and prostate, and hence, deleterious effects in these tissues are lessened to a degree.[6] This is because nandrolone is metabolized by 5α-reductase to the much weaker androgen 5α-dihydronandrolone (DHN), which has both reduced affinity for the androgen receptor (AR) relative to nandrolone in vitro and weaker androgenic activity in vivo.[6] The lack of alkylation on the 17α-carbon drastically reduces the hepatotoxic potential of nandrolone.[medical citation needed] Estrogenic effects resulting from reaction with aromatase are also reduced due to lessened enzyme interaction,[7] but effects such as gynaecomastia and reduced libido may still occur at sufficiently high doses. Other side effects of high doses 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 DHN in the penis since DHT is a known sexual modulator.

In addition to its androgenic/anabolic activity, unlike many other anabolic steroids, nandrolone is also a potent progestogen.[8] It binds to the progesterone receptor with approximately 22% of the affinity of progesterone.[8] The progestogenic activity of nandrolone may serve to augment its antigonadotropic potency.

Chemistry[edit]

Nandrolone is also known chemically as estra-4-en-17β-ol-3-one or 19-norandrost-4-en-17β-ol-3-one.[9] It is the 19-demethylated analogue of testosterone, and for this reason, is also known as 19-nortestosterone.[9][10]

Derivatives[edit]

Esters[edit]

A large number of nandrolone esters have been marketed and used clinically (see here for a full list).

Anabolic steroids[edit]

Nandrolone is the parent compound of a large group of anabolic steroids (see here and here for a list).

Progestins[edit]

Nandrolone is also the parent compound of a large group of progestins.[11][12] They are subdivided into two groups, the estranes and the gonanes.[11] The estranes include norethisterone (norethindrone), norethisterone acetate, norethisterone enanthate, lynestrenol, etynodiol diacetate, and noretynodrel, while the gonanes include norgestrel, levonorgestrel, desogestrel, etonogestrel, gestodene, norgestimate, dienogest, and norelgestromin.[11]

Synthesis[edit]

19-Nortestosterone synthesis:[13] alternative:[14][15]

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.

This reaction, now known as the Birch reduction,[16] 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 e.g., 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[edit]

Detection in body fluids[edit]

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,[19] 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.[20][21][22][23]

A number of nandrolone cases in athletics occurred in 1999, which included high-profile athletes such as Merlene Ottey, Dieter Baumann and Linford Christie.[24] 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.[25]

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.[26] 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.[27]

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

History[edit]

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

Nandrolone was first synthesized in 1950.[2][9][10][28] It was first introduced, as nandrolone phenylpropionate and then as nandrolone decanoate, in 1959 and 1962, respectively.[29]

Society and culture[edit]

Publicized abuse cases[edit]

See also[edit]

References[edit]

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  2. ^ a b c J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 660–. ISBN 978-1-4757-2085-3. 
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  12. ^ A. Wayne Meikle (24 April 2003). Endocrine Replacement Therapy in Clinical Practice. Springer Science & Business Media. pp. 489–. ISBN 978-1-59259-375-0. Estranes. Estrane and gonane progestogens are derived from 19-nortestosterone, the progestogenic parent compound used in oral contraceptives in the United States. Estranes are characterized by the presence of an ethinyl group at position 17 and by the absence of a methyl group between the A and B rings (see Fig. 10). The estrane progestogens that are related structurally to norethindrone (norethynodrel, lynestrenol, norethindrone acetate, ethynodiol diacetate) are converted to this parent compound. Norethindrone is the second most commonly used progestogen in the United States for HRT. Gonanes. The gonanes share the structural modifications found in the estranes and also possess an ethinyl group at position 13 and a keto group at position 3 (see Fig. 11). Norgestrel was synthesized in 1963 and is a racemic mixture of dextro and levorotatory forms. The levorotatory form, levonorgestrel, provides the biologic activity. Third-generation gonanes (desogestrel, gestodene, and norgestimate) have been developed to reduce unwanted side effects of progestogens, [...] 
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