Ethylestrenol

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 461097524

| IUPAC_name = (8R,9S,10R,13S,14S,17S)-17-ethyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol

| image = Ethylestrenol.svg

| image_class = skin-invert-image

| width = 215px

| tradename = Maxibolin, Orabolin, others

| Drugs.com = {{drugs.com|international|ethylestrenol}}

| pregnancy_category =

| legal_BR = C5

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

| legal_CA = Schedule IV

| legal_US = Schedule III

| legal_status =

| routes_of_administration = By mouth

| class = Androgen; Anabolic steroid; Progestogen

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| IUPHAR_ligand = 6948

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 965-90-2

| ATC_prefix = A14

| ATC_suffix = AB02

| PubChem = 13765

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01493

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 13168

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = ADC79EK5Q8

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01414

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 31578

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1200623

| synonyms = Ethyloestrenol; Ethylnandrol; ORG-483; 3-Deketo-17α-ethyl-19-nortestosterone; 17α-Ethylestr-4-en-17β-ol; 19-Nor-17α-pregn-4-en-17β-ol

| C=20 | H=32 | O=1

| SMILES = O[C@]2(CC[C@H]1[C@H]4[C@H](CC[C@@]12C)[C@@H]3\C(=C/CCC3)CC4)CC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C20H32O/c1-3-20(21)13-11-18-17-9-8-14-6-4-5-7-15(14)16(17)10-12-19(18,20)2/h6,15-18,21H,3-5,7-13H2,1-2H3/t15-,16+,17+,18-,19-,20-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = AOXRBFRFYPMWLR-XGXHKTLJSA-N

}}

Ethylestrenol, also known as ethyloestrenol or ethylnandrol and sold under the brand names Maxibolin and Orabolin among others, is an androgen and anabolic steroid (AAS) medication which has been used in the past for a variety of indications such as to promote weight gain and to treat anemia and osteoporosis but has been discontinued for use in humans.{{cite book|author=William Llewellyn|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT591|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=591–598}} It is still available for veterinary use in Australia and New Zealand however. It is taken by mouth.

Side effects of ethylestrenol include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire. It can also cause liver damage. The drug is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has strong anabolic effects relative to its androgenic effects. The drug also has strong progestogenic effects. Ethylestrenol is a prodrug of norethandrolone.

Ethylestrenol was first described in 1959 and was introduced for medical use in 1961. In addition to its medical use, ethylestrenol has been used to improve physique and performance. However, it is described as a very weak muscle-builder compared to other AAS and in relation to this has not been commonly used for such purposes. The drug is a controlled substance in many countries and so non-medical use is generally illicit.

Medical uses

Ethylestrenol has been used for a variety of indications including:

To promote weight gain and muscle growth
As an adjunct in the treatment of bone pain and decreased bone strength associated with osteoporosis{{cite book| vauthors = Colby HD, Longhurst PA | chapter = Fate of Anabolic Steroids in the Body| veditors = Thomas JA |title=Drugs, Athletes, and Physical Performance| chapter-url = https://books.google.com/books?id=9u0pBgAAQBAJ&pg=PA22|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-5499-4|pages=21–22}}
As an adjunct for catabolic states such as corticosteroid therapy and convalescence as in chronic infections, extensive surgery, and severe trauma
To treat treatment-refractory anemias (via stimulation of erythropoiesis) such as acquired and congenital aplastic anemia and anemia of chronic kidney disease
As an adjunct to improve strength and well-being in arthritis
To treat short stature in youth{{cite book| vauthors = Miller RL |title=The Encyclopedia of Addictive Drugs|url=https://books.google.com/books?id=G7As-qawdzMC&pg=PA156|year=2002|publisher=Greenwood Publishing Group|isbn=978-0-313-31807-8|pages=156–}}

Contraindications

Ethylestrenol should not be taken by pregnant women as it can masculinize female fetuses. It is contraindicated in men with prostate cancer as it may accelerate the progression of the disease.{{cite book| vauthors = Ebadi M | chapter = Ethylestrenol |title=Desk Reference of Clinical Pharmacology | edition = Second | chapter-url = https://books.google.com/books?id=ihxyHbnj3qYC&pg=PA257|date=31 October 2007|publisher=CRC Press|isbn=978-1-4200-4744-8|pages=257–}}

Side effects

Side effects of ethylestrenol include virilization among others.

Pharmacology

=Pharmacodynamics=

File:Norethandrolone structure.png (3-ketoethylestrenol), the active metabolite of ethylestrenol.]]

As an AAS, ethylestrenol is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT).{{cite journal | vauthors = Kicman AT | title = Pharmacology of anabolic steroids | journal = British Journal of Pharmacology | volume = 154 | issue = 3 | pages = 502–521 | date = June 2008 | pmid = 18500378 | pmc = 2439524 | doi = 10.1038/bjp.2008.165 }} It has low estrogenic activity (via aromatization into ethylestradiol following transformation into norethandrolone), strong progestogenic activity, and a high ratio of anabolic to androgenic activity, similarly to other nandrolone derivatives. Like other 17α-alkylated AAS, ethylestrenol has a risk of hepatotoxicity.

{{Relative affinities of nandrolone and related steroids at the androgen receptor}}

=Pharmacokinetics=

Ethylestrenol has very low affinity for human serum sex hormone-binding globulin (SHBG), less than 5% of that of testosterone and less than 1% of that of DHT.{{cite journal | vauthors = Saartok T, Dahlberg E, Gustafsson JA | title = Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin | journal = Endocrinology | volume = 114 | issue = 6 | pages = 2100–2106 | date = June 1984 | pmid = 6539197 | doi = 10.1210/endo-114-6-2100 }} It is known to be metabolized into the closely related AAS norethandrolone (17α-ethyl-19-nortestosterone) in the body and has been regarded as a prodrug of norethandrolone. This is in accordance with its very low affinity for the androgen receptor, only about 5% of that of testosterone and 2% of that of dihydrotestosterone.{{cite journal | vauthors = Bergink EW, Geelen JA, Turpijn EW | title = Metabolism and receptor binding of nandrolone and testosterone under in vitro and in vivo conditions | journal = Acta Endocrinologica. Supplementum | volume = 271 | issue = 3_Suppla | pages = 31–37 | date = 1985 | pmid = 3865479 | doi = 10.1530/acta.0.109S0031 }}

Chemistry

Ethylestrenol, also known as 3-deketo-17α-ethyl-19-nortestosterone or as 17α-ethylestr-4-en-17β-ol, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone (19-nortestosterone; 19-NT).{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA168|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=518–519}}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA415|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=415–}} It is specifically the 17α-ethyl and 3-deketo derivative of nandrolone as well as the 3-deketo derivative of norethandrolone (17α-ethyl-19-NT). Other related AAS include bolenol (3-deketo-17α-ethyl-19-nor-5-androstenediol), ethyldienolone (17α-ethyl-δ⁹-19-NT), norboletone (17α-ethyl-18-methyl-19-NT), propetandrol (17α-ethyl-19-NT 3β-propionate), and tetrahydrogestrinone (THG; 17α-ethyl-18-methyl-δ^9,11-19-NT). The progestins allylestrenol (3-deketo-17α-allyl-19-NT) and lynestrenol (3-deketo-17α-ethynyl-19-NT) are also closely related to ethylestrenol, differing only by the C17α substitution.

History

Ethylestrenol was described in the literature in 1959 and approved for medical use in 1961 and in the United States in 1964.{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia | edition = 3rd |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1513|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=1513–1514}}

Society and culture

=Generic names=

Ethylestrenol is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}, while éthylestrénol is its {{abbrlink|DCF|Dénomination Commune Française}} and ethylnandrol is its {{abbrlink|JAN|Japanese Accepted Name}}.{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA116|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=116–}}{{Cite web |url=https://www.drugs.com/international/ethylestrenol.html |title= Ethylestrenol | work = Drugs.com |access-date=2017-11-10 |archive-date=2017-11-11 |archive-url=https://web.archive.org/web/20171111042015/https://www.drugs.com/international/ethylestrenol.html |url-status=dead }} The {{abbrlink|BAN|British Approved Name}} was formerly ethyloestrenol, but it was eventually changed.

=Brand names=

Ethylestrenol is or has been marketed under a variety of brand names including Durabolin O, Duraboral, Fertabolin, Maxibolin, Maxibolin Elixir, Orabolin, Orgabolin, Orgaboral, and Virastine. The brand name Durabolin O is a contraction of "Durabolin Oral", Durabolin being a brand name of the nandrolone ester nandrolone phenylpropionate. Ethylestrenol is or has also been marketed for veterinary use under the brand names Nandoral, Nitrotain, and Oestrotain.

=Availability=

The availability of ethylestrenol is very limited. It appears to be available only in Australia and New Zealand and in these countries only for veterinary use.

=Legal status=

Ethylestrenol, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act.{{cite book| vauthors = Bono JP | chapter = Criminalistics: Introduction to Controlled Substances| veditors = Karch SB |title=Drug Abuse Handbook | edition = Second | chapter-url = https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30 |date=21 December 2006|publisher=CRC Press|isbn=978-1-4200-0346-8|pages=30–}}