Mestanolone

{{Short description|Chemical compound}} {{Distinguish|Mesterolone}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 459508888 | IUPAC_name = (5''S'',8''R'',9''S'',10''S'',13''S'',14''S'',17''S'')-17-hydroxy-10,13,17-trimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1''H''-cyclopenta[''a'']phenanthren-3-one | image = Mestanolone Structural Formula V2.svg | image_class = skin-invert-image | width = 225px

| tradename = Androstalone, Ermalone, others | Drugs.com = {{drugs.com|international|mestanolone}} | pregnancy_US = X | legal_US = Schedule III | routes_of_administration = By mouth | class = Androgen; Anabolic steroid

| CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 521-11-9 | ATC_prefix = None | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 261514 | PubChem = 10633 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10187 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = S712YZ168E | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01533 | synonyms = RU-143; Methylandrostanolone; Methyldihydrotestosterone; Methyl-DHT; 17α-Methyl-4,5α-dihydrotestosterone; 17α-Methyl-DHT; 17α-Methyl-5α-androstan-17β-ol-3-one;

| C=20 | H=32 | O=2 | SMILES = O=C2C[C@@H]1CC[C@@H]3[C@@H]([C@@]1(C)CC2)CC[C@]4([C@H]3CC[C@@]4(O)C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C20H32O2/c1-18-9-6-14(21)12-13(18)4-5-15-16(18)7-10-19(2)17(15)8-11-20(19,3)22/h13,15-17,22H,4-12H2,1-3H3/t13-,15+,16-,17-,18-,19-,20-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = WYZDXEKUWRCKOB-YDSAWKJFSA-N }}

'''Mestanolone''', also known as '''methylandrostanolone''' and sold under the brand names '''Androstalone''' and '''Ermalone''' among others, is an androgen and anabolic steroid (AAS) medication which is mostly no longer used.<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=PA775|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=775–}}</ref><ref name="IndexNominum2000">{{cite book | chapter = Mestanolone |title=Index Nominum 2000: International Drug Directory| chapter-url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA655 |year=2000 |publisher=Taylor & Francis |isbn=978-3-88763-075-1 |pages=655–}}</ref><ref name="Drugs.com" /><ref name="Llewellyn2009">{{cite book| vauthors = Llewellyn W |title= Anabolics |url= https://books.google.com/books?id=afKLA-6wW0oC |year=2009 |publisher=Molecular Nutrition Llc|isbn=978-0967930473|pages=241}}</ref> It is still available for use in Japan however.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is taken by mouth.<ref name="Llewellyn2009" />

Side effects of mestanolone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.<ref name="Llewellyn2009" /> It can also cause liver damage.<ref name="Llewellyn2009" /> 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="Llewellyn2009" /><ref name="pmid18500378">{{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 strong androgenic effects and weak anabolic effects, which make it useful for producing masculine psychological and behavioral effects.<ref name="Llewellyn2009" /> The drug has no estrogenic effects.<ref name="Llewellyn2009" />

Mestanolone was discovered in 1935 and was introduced for medical use in the 1950s.<ref name="pmid8674183" /><ref name="RuzickaGoldberg1935" /><ref name="pmid14086172" /><ref name="Llewellyn2009" /> In addition to its medical use, mestanolone has been used to improve physique and performance.<ref name="Llewellyn2009" /> It was used in East Germany in Olympic athletes as part of a state-sponsored doping program in the 1970s and 1980s.<ref name="Llewellyn2009" /> The drug is a controlled substance in many countries and so non-medical use is generally illicit.<ref name="Llewellyn2009" />

==Medical uses== ===Available forms=== Mestanolone was available in the form of 25 mg sublingual tablets (brand name Ermalone).<ref name="Krüskemper2013">{{cite book | vauthors = Krüskemper HL |title=Anabolic Steroids|url=https://books.google.com/books?id=4xIlBQAAQBAJ&pg=PA196|date=22 October 2013|publisher=Elsevier|isbn=978-1-4832-6504-9|pages=196–}}</ref>

==Side effects== {{See also|Anabolic steroid#Adverse effects}}

Side effects of mestanolone include virilization and hepatotoxicity among others.<ref name="Llewellyn2009" />

==Pharmacology== ===Pharmacodynamics=== Mestanolone is an AAS, with both androgenic and anabolic effects.<ref name="Llewellyn2009" /> It is very similar in its effects to androstanolone (dihydrotestosterone; DHT), and can be thought of as an orally active version of this AAS.<ref name="Llewellyn2009" /> Due to inactivation by 3α-hydroxysteroid dehydrogenase (3α-HSD) in skeletal muscle, mestanolone is described as a very poor anabolic agent, similarly to androstanolone and mesterolone.<ref name="Llewellyn2009" /> As mestanolone is 5α-reduced, it cannot be aromatized and hence has no propensity for estrogenic side effects such as gynecomastia.<ref name="Llewellyn2009" /> The drug also has no progestogenic activity.<ref name="Llewellyn2009" /> Like other 17α-alkylated AAS, mestanolone is hepatotoxic.<ref name="Llewellyn2009" />

===Pharmacokinetics=== Due to its C17α methyl group, unlike androstanolone, mestanolone is orally active.<ref name="Llewellyn2009" />

==Chemistry== {{See also|List of androgens/anabolic steroids}}

Mestanolone, also known as 17α-methyl-4,5α-dihydrotestosterone (17α-methyl-DHT) or as 17α-methyl-5α-androstan-17β-ol-3-one, is a synthetic androstane steroid and a 17α-alkylated derivative of dihydrotestosterone (DHT).<ref name="Elks2014" /><ref name="Llewellyn2009" /> It differs from DHT only by the presence of the methyl group at the C17α position.<ref name="Elks2014" /><ref name="Llewellyn2009" /> Close synthetic relatives of mestanolone include oxandrolone (2-oxa-17α-methyl-DHT), oxymetholone (2-hydroxymethylene-17α-methyl-DHT), and stanozolol (a derivative of 17α-methyl-DHT (mestanolone) with a pyrazole ring fused to the A ring).<ref name="Elks2014" /><ref name="Llewellyn2009" />

===Synthesis=== The chemical synthesis of mestanolone was reported:<ref>廖俊, et al. CN109627273 (2019 to HUAZHONG PHARMACEUTICAL CO Ltd).</ref> Although the Lednicer book method uses DHEA as the starting material,<ref>{{cite book | vauthors=((Lednicer, D.)) | date= 2011 | title=Steroid chemistry at a glance | publisher=Wiley | series=Chemistry at a glance | edition=1. publ | isbn=9780470660843}}</ref> androstenedione is cheaper and more readily available.

center|500px|class=skin-invert-image

The reaction of Androstenedione [63-05-8] ('''1''') with triethyl orthoformate convers the enone into the corresponding enol ether, 3-Ethoxyandrosta-3,5-dien-17-one [972-46-3] ('''2'''). Grignard addition of methyl magnesium halide gives ('''3'''). Catalytic hydrogenation reduces the C5=C6 olefin giving ('''4'''). Hydrolysis of the product in aqueous acid completed the synthesis of mestanolone ('''5'''). ===Applications=== Mestanolone is used in the chemical synthesis of Methyl-1-testosterone, which in-turn is used to make oxandrolone.

Mestanolone is also used to make Oxymesterone, Methyldiazirinol & Furazabol.

Another use is in the synthesis of Oxymetholone, a compound which itself finds use in the synthesis of stanozolol, Cyanostane, Androisoxazole & Methasterone.

==History== Mestanolone was first synthesized in 1935 along with methyltestosterone and methandriol.<ref name="pmid8674183">{{cite journal | vauthors = Schänzer W | title = Metabolism of anabolic androgenic steroids | journal = Clinical Chemistry | volume = 42 | issue = 7 | pages = 1001–1020 | date = July 1996 | pmid = 8674183 | doi = 10.1093/clinchem/42.7.1001 | doi-access = free }}</ref><ref name="RuzickaGoldberg1935">{{cite journal| vauthors = Ruzicka L, Goldberg MW, Rosenberg HR |title=Sexualhormone X. Herstellung des 17-Methyl-testosterons und anderer Androsten- und Androstanderivate. Zusammenhänge zwischen chemischer Konstitution und männlicher Hormonwirkung|journal=Helvetica Chimica Acta|volume=18|issue=1|year=1935|pages=1487–1498|issn=0018-019X|doi=10.1002/hlca.193501801203}}</ref> It was developed by Roussel in the 1950s and was introduced for medical use, under the brand names Androstalone and Ermalone, by at least 1960.<ref name="Llewellyn2009" /><ref name="pmid13800998">{{cite journal | vauthors = Bishop PM | title = Male sex hormones | journal = British Medical Journal | volume = 1 | issue = 5167 | pages = 184–186 | date = January 1960 | pmid = 13800998 | pmc = 1966335 | doi = 10.1136/bmj.1.5167.184 }}</ref><ref name="pmid14086172">{{cite journal | vauthors = Arnold A, Potts GO, Beyler AL | title = The Ratio of Anabolic to Androgenic Activity of 7: 17-Dimethyltestosterone, Oxymesterone, Mestanolone and Fluoxymesterone | journal = The Journal of Endocrinology | volume = 28 | pages = 87–92 | date = December 1963 | pmid = 14086172 | doi = 10.1677/joe.0.0280087 }}</ref> It was marketed in Germany.<ref name="Llewellyn2009" /> The drug was originally thought to be a potent anabolic agent, but subsequent research showed that it actually has relatively weak anabolic effects and is mostly an androgen.<ref name="Llewellyn2009" /> Mestanolone was used as a doping agent in athletes competing in the Olympics from East Germany due to a state-sponsored doping program in the 1970s and 1980s.<ref name="Llewellyn2009" /> Its value is said to have been less as a muscle-builder and more as an androgen in the central nervous system and neuromuscular interaction, improving speed, strength, aggression, focus, endurance, and stress resilience.<ref name="Llewellyn2009" /> Today, mestanolone has mostly been discontinued in medicine, though it is still available in Japan.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Llewellyn2009" />

==Society and culture== ===Generic names=== ''Mestanolone'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014" /><ref name="ChemIDplus">{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/#tab/sidsrcname=ChemIDplus&query=521-11-9&input_type=text| work = ChemIDplus | title = Mestanolone [INN:BAN:JAN] | publisher = U.S. National Library of Medicine }}</ref>

===Brand names=== Mestanolone was marketed under the brand names Andoron, Androstalone, Ermalone, Mesanolon, and Notandron among many others.<ref name="Llewellyn2009" /><ref name="IndexNominum2000" /><ref name="Negwer1987">{{cite book| vauthors = Negwer M |title=Organic-chemical Drugs and Their Synonyms: (an International Survey)|url=https://books.google.com/books?id=k6fwAAAAMAAJ|year=1987|publisher=VCH Publishers|isbn=978-0-89573-552-2|quote=Anavormol, Andoron, Androne, Androstalone, Antalon “Kobayashi K.”, Assimil, Ermalone, Etnabolate, Hermalone-Glosset, Macrobin (Tabl. -- Syrup), Mesanolon, Mestalone, Mestanolone”, Methyantalon, Methybol, 172-Methylandrostanolone, Preroide,. 1045.}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/mestanolone.html|title = S1. Anabolic Agents | work = Drugs in Sport: Anti-Doping Prohibited List | via = Drugs.com }}</ref>

===Availability=== Mestanolone has mostly been discontinued but remains available in Japan.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Llewellyn2009" />

==References== {{Reflist}}

Category:Abandoned drugs Category:Tertiary alcohols Category:Androgens Category:Androstanes Category:Hepatotoxins Category:Human drug metabolites Category:Ketones