{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 461097524 | IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''S'')-17-ethyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-17-ol | image = Ethylestrenol.svg | image_class = skin-invert-image | width = 215px
<!--Clinical data--> | tradename = Maxibolin, Orabolin, others | Drugs.com = {{drugs.com|international|ethylestrenol}} | pregnancy_category = | legal_BR = C5 | legal_BR_comment = <ref>{{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}}</ref> | legal_CA = Schedule IV | legal_US = Schedule III | legal_status = | routes_of_administration = By mouth | class = Androgen; Anabolic steroid; Progestogen
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | 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
<!--Chemical data--> | 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 }} <!-- Definition and medical uses --> '''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.<ref name="Llewellyn2011">{{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}}</ref> It is still available for veterinary use in Australia and New Zealand however.<ref name="Drugs.com" /> It is taken by mouth.<ref name="Llewellyn2011" />
<!-- Side effects and mechanism of action --> Side effects of ethylestrenol include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.<ref name="Llewellyn2011" /> It can also cause liver damage.<ref name="Llewellyn2011" /> 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).<ref name="Llewellyn2011" /><ref name="Kicman2008" /> It has strong anabolic effects relative to its androgenic effects.<ref name="Llewellyn2011" /> The drug also has strong progestogenic effects.<ref name="Llewellyn2011" /> Ethylestrenol is a prodrug of norethandrolone.<ref name="Llewellyn2011" />
<!-- History, society, and culture --> Ethylestrenol was first described in 1959 and was introduced for medical use in 1961.<ref name="Elks2014" /><ref name="Llewellyn2011" /><ref name="Publishing2013" /> In addition to its medical use, ethylestrenol has been used to improve physique and performance.<ref name="Llewellyn2011" /> 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.<ref name="Llewellyn2011" /> The drug is a controlled substance in many countries and so non-medical use is generally illicit.<ref name="Llewellyn2011" />
==Medical uses== Ethylestrenol has been used for a variety of indications including:<ref name="Llewellyn2011" />
* To promote weight gain and muscle growth<ref name="Ebadi2007" /> * As an adjunct in the treatment of bone pain and decreased bone strength associated with osteoporosis<ref name="Thomas2012">{{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}}</ref> * As an adjunct for catabolic states such as corticosteroid therapy and convalescence as in chronic infections, extensive surgery, and severe trauma<ref name="Ebadi2007" /><ref name="Thomas2012" /> * To treat treatment-refractory anemias (via stimulation of erythropoiesis) such as acquired and congenital aplastic anemia and anemia of chronic kidney disease<ref name="Ebadi2007" /><ref name="Thomas2012" /> * As an adjunct to improve strength and well-being in arthritis<ref name="Thomas2012" /> * To treat short stature in youth<ref name="Miller2002">{{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–}}</ref>
==Contraindications== Ethylestrenol should not be taken by pregnant women as it can masculinize female fetuses.<ref name="Miller2002" /> It is contraindicated in men with prostate cancer as it may accelerate the progression of the disease.<ref name="Ebadi2007">{{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–}}</ref>
==Side effects== {{See also|Anabolic steroid#Adverse effects}}
Side effects of ethylestrenol include virilization among others.<ref name="Llewellyn2011" />
==Pharmacology==
===Pharmacodynamics=== [[File:Norethandrolone structure.png|class=skin-invert-image|thumb|right|235px|Norethandrolone (3-ketoethylestrenol), the active metabolite of ethylestrenol.]] {{Relative androgenic to anabolic activity in animals}}
As an AAS, ethylestrenol is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT).<ref name="Llewellyn2011" /><ref name="Kicman2008">{{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 }}</ref> 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.<ref name="Llewellyn2011" /> Like other 17α-alkylated AAS, ethylestrenol has a risk of hepatotoxicity.<ref name="Llewellyn2011" />
{{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.<ref name="pmid6539197">{{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 }}</ref> 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.<ref name="Llewellyn2011" /> 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.<ref name="pmid3865479">{{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 }}</ref>
==Chemistry== {{See also|List of androgens/anabolic steroids}}
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).<ref name="Elks2014">{{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}}</ref><ref name="IndexNominum2000">{{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–}}</ref><ref name="Llewellyn2011" /> 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).<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Llewellyn2011" /> Other related AAS include bolenol (3-deketo-17α-ethyl-19-nor-5-androstenediol), ethyldienolone (17α-ethyl-δ<sup>9</sup>-19-NT), norboletone (17α-ethyl-18-methyl-19-NT), propetandrol (17α-ethyl-19-NT 3β-propionate), and tetrahydrogestrinone (THG; 17α-ethyl-18-methyl-δ<sup>9,11</sup>-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.<ref name="Elks2014" /><ref name="Llewellyn2011" /><ref name="Publishing2013">{{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}}</ref>
==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}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012">{{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–}}</ref><ref name="Drugs.com">{{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 }}</ref> The {{abbrlink|BAN|British Approved Name}} was formerly ''ethyloestrenol'', but it was eventually changed.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" />
===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.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Llewellyn2011" /> The brand name Durabolin O is a contraction of "Durabolin Oral", Durabolin being a brand name of the nandrolone ester nandrolone phenylpropionate.<ref name="Llewellyn2011" /> Ethylestrenol is or has also been marketed for veterinary use under the brand names Nandoral, Nitrotain, and Oestrotain.<ref name="Drugs.com" /><ref name="Llewellyn2011" />
===Availability=== The availability of ethylestrenol is very limited.<ref name="Llewellyn2011" /><ref name="IndexNominum2000" /><ref name="Drugs.com" /> It appears to be available only in Australia and New Zealand and in these countries only for veterinary use.<ref name="Llewellyn2011" /><ref name="Drugs.com" />
===Legal status=== Ethylestrenol, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act.<ref name="FFFLM2006">{{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–}}</ref>
== References == {{Reflist}}
== External links ==
{{Navboxes | title = Medical uses | titlestyle = background:#ccccff | list1 = {{Androgens and antiandrogens}} {{Estrogens and antiestrogens}} {{Progestogens and antiprogestogens}} }} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{Androgen receptor modulators}} {{Estrogen receptor modulators}} {{Progesterone receptor modulators}} }}
Category:Abandoned drugs Category:1-Ethylcyclopentanols Category:Androgens Category:Estranes Category:Hepatotoxins Category:Sex hormone esters and conjugates Category:Progestogens Category:Synthetic estrogens Category:Veterinary drugs