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Oxendolone

From Wikipedia, the free encyclopedia
Chemical compound
Not to be confused withOxandrolone.
Pharmaceutical compound
Oxendolone
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]
Eliminationhalf-lifeIMTooltip Intramuscular injection: 5.0–6.6 days.[4][6]
Identifiers
  • (9S,14S,17S)-16-ethyl-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one
CAS Number
PubChemCID
ChemSpider
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC20H30O2
Molar mass302.458 g·mol−1
3D model (JSmol)
  • CCC1CC2C3CCC4=CC(=O)CCC4C3CCC2(C1O)C
  • InChI=1S/C20H30O2/c1-3-12-11-18-17-6-4-13-10-14(21)5-7-15(13)16(17)8-9-20(18,2)19(12)22/h10,12,15-19,22H,3-9,11H2,1-2H3/t12?,15?,16-,17?,18+,19+,20?/m1/s1
  • Key:FCKLFGKATYPJPG-LNRSQMQGSA-N

Oxendolone, sold under the brand namesProstetin andRoxenone, is anantiandrogen andprogestin medication which is used inJapan in the treatment ofenlarged prostate.[7][8][9][10][11] However, this use is controversial due to concerns about its clinical efficacy.[11] Oxendolone is not effectiveby mouth and must be given byinjection into muscle.[5][1][2][3][4]

Oxendolone is anantiandrogen, and hence is anantagonist of theandrogen receptor, thebiological target of androgens liketestosterone anddihydrotestosterone.[12][13][14][15][6] It is also a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[12][13][14][15] Due to its progestogenic activity, oxendolone hasantigonadotropic effects.[16][17] Oxendolone has no other importanthormonal activity...

Oxendolone was introduced for medical use in 1981.[8] It is used only in Japan.[8][11]

Medical uses

[edit]

Oxendolone is used in the treatment ofbenign prostatic hyperplasia (BPH) inJapan.[8][11] It has been used at a dosage of 200 mg once every 2 weeks viaintramuscular 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 inclinical trials.[11]

Side effects

[edit]
See also:Antiandrogen § Side effects, andProgestin § Side effects

Pharmacology

[edit]

Pharmacodynamics

[edit]

Oxendolone binds to theandrogen receptor (Ki = 320 nM) andprogesterone receptor (Ki = 20 nM) and acts as a weak but clinically relevantinhibitor of5α-reductase (IC50Tooltip half-maximal inhibitory concentration = 1.4 μM).[12][13][14][15] Therelative binding affinity of oxendolone for the androgen receptor is 0.8 to 3.6% of that ofmetribolone.[18][19] Oxendolone is not asilent antagonist of the androgen receptor but is rather predominantly antagonistic with weakagonistic activity;[13] for this reason, it has been described as aselective androgen receptor modulator.[20] The medication has potentantigonadotropic effects via its progestogenic activity.[16] It has been found to suppressluteinizing hormone andtestosterone levels to an equivalent extent asallylestrenol andchlormadinone acetate, which are two progestins that are similarly used at high doses to treat BPH.[17]

Pharmacokinetics

[edit]

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

Chemistry

[edit]
See also:List of progestogens,Steroidal antiandrogen, andList of steroidal antiandrogens

Oxendolone, also known as 16β-ethyl-19-nortestosterone or 16β-ethylestr-4-en-17β-ol-3-one, is asyntheticestranesteroid and aderivative oftestosterone and19-nortestosterone (nandrolone).[7][8]

Theacetateester of oxendolone is known as TSAA-328, while thecaproate ester of oxendolone is known as TSAA-330.[21] They were never marketed.[21]

History

[edit]

Oxendolone has been marketed inJapan byTakeda since 1981.[8]

Society and culture

[edit]

Generic names

[edit]

Oxendolone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name, andJANTooltip Japanese Accepted Name.[7][22] It is also known by its developmental code nameTSAA-291.[7][22]

Brand names

[edit]

Oxendolone is or has been sold under the brand names Prostetin and Roxenone.[7][22]

Availability

[edit]

Oxendolone is marketed only inJapan.[22]

References

[edit]
  1. ^abcHenkler G, Klotzbach M, Koch H, Müller W, Richter J (November 1982). "[Progress in the area of drug development. 15]".Die Pharmazie (in German).37 (11):753–765.PMID 6131442.[Oxendolone] has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy.
  2. ^abcHikichi Y, Yamaoka M, Kusaka M, Hara T (October 2015). "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile".European Journal of Pharmacology.765:322–331.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. ^abcOstri P, Swartz R, Meyhoff HH, Petersen JH, Lindgård G, Frimodt-Møller C, et al. (1989). "Antiandrogenic treatment of benign prostatic hyperplasia: a placebo controlled trial".Urological Research.17 (1):29–33.doi:10.1007/bf00261046.PMID 2466359.S2CID 30551043.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. ^abcdeMidgley I, Fowkes AG, Darragh A, Lambe R, Chasseaud LF, Taylor T (April 1983). "The metabolic fate of the anti-androgenic agent, oxendolone, in man".Steroids.41 (4):521–536.doi:10.1016/0039-128x(83)90092-2.PMID 6419414.S2CID 41224726.After intramuscular administration of 16β-ethyl-17β-hydroxy-4-[4-14C] estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, [...]
  5. ^abcIga K (7 November 2002)."Slowly Disintegrating Buccal Mucoadhesive Pain-Tablet (S-DBMP-T) and Buccal Covered=Tablet System (BCTS)". In Rathbone MJ, Hadgraft J, Roberts MS (eds.).Modified-Release Drug Delivery Technology. CRC Press. pp. 368–.ISBN 978-0-8247-0869-6.
  6. ^abGao W, Bohl CE, Dalton JT (September 2005)."Chemistry and structural biology of androgen receptor".Chemical Reviews.105 (9):3352–3370.doi:10.1021/cr020456u.PMC 2096617.PMID 16159155.
  7. ^abcdeElks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 914–.ISBN 978-1-4757-2085-3.
  8. ^abcdefWilliam Andrew Publishing (22 October 2013).Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 2935–.ISBN 978-0-8155-1856-3.
  9. ^Negwer M, Scharnow HG (2001).Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. p. 2023.ISBN 978-3-527-30247-5.
  10. ^Tan MH, Li J, Xu HE, Melcher K, Yong EL (January 2015)."Androgen receptor: structure, role in prostate cancer and drug discovery".Acta Pharmacologica Sinica.36 (1):3–23.doi:10.1038/aps.2014.18.PMC 4571323.PMID 24909511.
  11. ^abcdeIshizuka O, Nishizawa O, Hirao Y, Ohshima S (November 2002)."Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy".International Journal of Urology.9 (11):607–612.doi:10.1046/j.1442-2042.2002.00539.x.PMID 12534901.
  12. ^abcMallamo JP, Juniewicz PE (8 September 1989)."New horizons in the treatment of proliferative prostatic disease". In Johns WS (ed.).Annual Reports in Medicinal Chemistry. Vol. 24. Academic Press. pp. 199–.doi:10.1016/S0065-7743(08)60543-6.ISBN 978-0-08-058368-6.
  13. ^abcdAnnual report of Shionogi Research Laboratories. 1991. pp. 76–77.
  14. ^abcKirby RS, Christmas T (1991). "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).doi:10.1007/BF00184713.ISSN 0724-4983.S2CID 38790542.
  15. ^abcBashirelahi N, Ganesan S, Ekiko DB, Young JD, Shida K, Yamanaka H, Takahashi E (September 1986). "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.doi:10.1016/0022-4731(86)90249-9.PMID 2430141.
  16. ^abSudo K, Yamazaki I, Masuoka M, Nakayama R (1979). "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.doi:10.1530/acta.0.092S053.PMID 294107.
  17. ^abcKatayama T, Umeda K, Kazama T (November 1986). "[Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy]".Hinyokika Kiyo. Acta Urologica Japonica (in Japanese).32 (11):1584–1589.PMID 2435122.
  18. ^Dalton J, Gao W (2010). "Androgen Receptor".Nuclear Receptors: Current Concepts and Future Challenges. Proteins and Cell Regulation. Springer. pp. 143–182.doi:10.1007/978-90-481-3303-1_6.ISBN 978-90-481-3302-4.
  19. ^Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens".Journal of Steroid Biochemistry.15:355–359.doi:10.1016/0022-4731(81)90297-1.PMID 7339263.
  20. ^Hikichi Y, Yamaoka M, Kusaka M, Hara T (October 2015). "Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile".European Journal of Pharmacology.765:322–331.doi:10.1016/j.ejphar.2015.08.052.PMID 26335395.
  21. ^abMasuoka M, Masaki T, Yamazaki I, Hori T, Nakayama R (1979). "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.doi:10.1530/acta.0.092s036.PMID 294106.
  22. ^abcd"Oxandrolone Uses, Side Effects & Warnings".Drugs.com.
Androgens
(incl.AASTooltip anabolic–androgenic steroid)
ARTooltip Androgen receptoragonists
Progonadotropins
Antiandrogens
ARTooltip Androgen receptorantagonists
Steroidogenesis
inhibitors
5α-Reductase
Others
Antigonadotropins
Others
Progestogens
(andprogestins)
PRTooltip Progesterone receptoragonists
Antiprogestogens
SPRMsTooltip Selective progesterone receptor modulators
PRTooltip Progesterone receptorantagonists
ARTooltip Androgen receptor
Agonists
SARMsTooltip Selective androgen receptor modulator
Antagonists
GPRC6A
Agonists
PRTooltip Progesterone receptor
Agonists
Mixed
(SPRMsTooltip Selective progesterone receptor modulators)
Antagonists
mPRTooltip Membrane progesterone receptor
(PAQRTooltip Progestin and adipoQ receptor)
Agonists
Antagonists
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