Chemistry:Oxendolone

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Short description: Chemical compound
Oxendolone
Oxendolone.svg
Clinical data
Trade namesProstetin, Roxenone
Other namesTSAA-291; 16β-Ethyl-19-nortestosterone; 16β-Ethylestr-4-en-17β-ol-3-one
Routes of
administration		Intramuscular injection[1][2][3][4]
Drug classSteroidal antiandrogen; Progestogen; Progestin
Pharmacokinetic data
BioavailabilityOral: Very low (1% in dogs)[5]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC20H30O2
Molar mass302.458 g·mol−1
3D model (JSmol)

Oxendolone, sold under the brand names Prostetin and Roxenone, is an antiandrogen and progestin medication which is used in Japan in the treatment of enlarged prostate.[6][7][8][9][10] However, this use is controversial due to concerns about its clinical efficacy.[10] Oxendolone is not effective by mouth and must be given by injection into muscle.[5][1][2][3][4]

Oxendolone is an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[11][12][13][14][15] It is also a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[11][12][13][14] Due to its progestogenic activity, oxendolone has antigonadotropic effects.[16][17] Oxendolone has no other important hormonal activity...

Oxendolone was introduced for medical use in 1981.[7] It is used only in Japan.[7][10]

Medical uses

Oxendolone is used in the treatment of benign prostatic hyperplasia (BPH) in Japan .[7][10] It has been used at a dosage of 200 mg once every 2 weeks via intramuscular injection.[17] Although it is approved for the treatment of BPH in Japan, concerns have been raised about its use for this condition due to poor efficacy seen in clinical trials.[10]

Side effects

Pharmacology

Pharmacodynamics

Oxendolone binds to the androgen receptor (Ki = 320 nM) and progesterone receptor (Ki = 20 nM) and acts as a weak but clinically relevant inhibitor of 5α-reductase (IC50 = 1.4 μM).[11][12][13][14] The relative binding affinity of oxendolone for the androgen receptor is 0.8 to 3.6% of that of metribolone.[18][19] Oxendolone is not a silent antagonist of the androgen receptor but is rather predominantly antagonistic with weak agonistic activity;[12] for this reason, it has been described as a selective androgen receptor modulator.[20] The medication has potent antigonadotropic effects via its progestogenic activity.[16] It has been found to suppress luteinizing hormone and testosterone levels to an equivalent extent as allylestrenol and chlormadinone acetate, which are two progestins that are similarly used at high doses to treat BPH.[17]

Pharmacokinetics

The oral bioavailability of oxendolone in dogs is extremely low, 1% at most.[5] Due to its low oral bioavailability, oxendolone is administered by intramuscular injection in humans.[1][2][3][4] Its elimination half-life via this route is 5.0 to 6.6 days.[4]

Chemistry

Oxendolone, also known as 16β-ethyl-19-nortestosterone or 16β-ethylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone and 19-nortestosterone (nandrolone).[6][7]

The acetate ester of oxendolone is known as TSAA-328, while the caproate ester of oxendolone is known as TSAA-330.[21] They were never marketed.[21]

History

Oxendolone has been marketed in Japan by Takeda since 1981.[7]

Society and culture

Generic names

Oxendolone is the generic name of the drug and its INN, USAN, and JAN.[6][22] It is also known by its developmental code name TSAA-291.[6][22]

Brand names

Oxendolone is or has been sold under the brand names Prostetin and Roxenone.[6][22]

Availability

Oxendolone is marketed only in Japan .[22]

References

  1. ↑ 1.0 1.1 1.2 "[Progress in the area of drug development. 15]" (in de). Die Pharmazie 37 (11): 753–765. November 1982. PMID 6131442. "[Oxendolone] has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy.". 
  2. ↑ 2.0 2.1 2.2 "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile". European Journal of Pharmacology 765: 322–331. October 2015. doi:10.1016/j.ejphar.2015.08.052. PMID 26335395. "According to the clinical data of TSAA-291, the plasma level of TSAA-291 after weekly intramuscular administration at 400 mg/kg for 12 weeks is approximately 100 nM (Drug Information).". 
  3. ↑ 3.0 3.1 3.2 "Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial". Urological Research 17 (1): 29–33. 1989. doi:10.1007/bf00261046. PMID 2466359. "Thirty patients were treated with weekly injections of oxendolone 200 mg during a 3 months' period, and 30 patients were allocated to placebo treatment.". 
  4. ↑ 4.0 4.1 4.2 4.3 "The metabolic fate of the anti-androgenic agent, oxendolone, in man". Steroids 41 (4): 521–536. April 1983. doi:10.1016/0039-128x(83)90092-2. PMID 6419414. "After intramuscular administration of 16β-ethyl-17β-hydroxy-4-[4-14C] estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, [...]". 
  5. ↑ 5.0 5.1 5.2 "Slowly Disintegrating Buccal Mucoadhesive Pain-Tablet (S-DBMP-T) and Buccal Covered=Tablet System (BCTS)". Modified-Release Drug Delivery Technology. CRC Press. 7 November 2002. pp. 368–. ISBN 978-0-8247-0869-6. https://books.google.com/books?id=mw9W82MLYZ8C&pg=PA368. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 914–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA914. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 2935–. ISBN 978-0-8155-1856-3. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA129. 
  8. ↑ Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. 2001. p. 2023. ISBN 978-3-527-30247-5. https://books.google.com/books?id=zmpqAAAAMAAJ. 
  9. ↑ "Androgen receptor: structure, role in prostate cancer and drug discovery". Acta Pharmacologica Sinica 36 (1): 3–23. January 2015. doi:10.1038/aps.2014.18. PMID 24909511. 
  10. ↑ 10.0 10.1 10.2 10.3 10.4 "Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy". International Journal of Urology 9 (11): 607–612. November 2002. doi:10.1046/j.1442-2042.2002.00539.x. PMID 12534901. 
  11. ↑ 11.0 11.1 11.2 "New horizons in the treatment of proliferative prostatic disease". Annual Reports in Medicinal Chemistry. 24. Academic Press. 8 September 1989. pp. 199–. doi:10.1016/S0065-7743(08)60543-6. ISBN 978-0-08-058368-6. https://books.google.com/books?id=HrALiG-4t7UC&pg=PA199. 
  12. ↑ 12.0 12.1 12.2 12.3 Annual report of Shionogi Research Laboratories. 1991. pp. 76–77. https://books.google.com/books?id=kR40AAAAIAAJ. 
  13. ↑ 13.0 13.1 13.2 "The potential value of 5-alpha-reductase inhibition in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia". World Journal of Urology 9 (1). 1991. doi:10.1007/BF00184713. ISSN 0724-4983. 
  14. ↑ 14.0 14.1 14.2 "Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate". Journal of Steroid Biochemistry 25 (3): 367–374. September 1986. doi:10.1016/0022-4731(86)90249-9. PMID 2430141. 
  15. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named GaoBohl2005
  16. ↑ 16.0 16.1 "Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins". Acta Endocrinologica. Supplementum 229 (3 Supplb): 53–66. 1979. doi:10.1530/acta.0.092S053. PMID 294107. 
  17. ↑ 17.0 17.1 17.2 "[Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy]" (in ja). Hinyokika Kiyo. Acta Urologica Japonica 32 (11): 1584–1589. November 1986. PMID 2435122. 
  18. ↑ "Androgen Receptor". Nuclear Receptors: Current Concepts and Future Challenges. Proteins and Cell Regulation. Springer. 2010. pp. 143–182. doi:10.1007/978-90-481-3303-1_6. ISBN 978-90-481-3302-4. 
  19. ↑ "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". Journal of Steroid Biochemistry 15: 355–359. December 1981. doi:10.1016/0022-4731(81)90297-1. PMID 7339263. 
  20. ↑ "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile". European Journal of Pharmacology 765: 322–331. October 2015. doi:10.1016/j.ejphar.2015.08.052. PMID 26335395. 
  21. ↑ 21.0 21.1 "Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives". Acta Endocrinologica. Supplementum 229: 36–52. 1979. doi:10.1530/acta.0.092s036. PMID 294106. 
  22. ↑ 22.0 22.1 22.2 22.3 "Oxandrolone Uses, Side Effects & Warnings". Drugs.com. https://www.drugs.com/international/oxendolone.html. 



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