Oxendolone

Last updated
Oxendolone
Oxendolone.svg
Clinical data
Trade names Prostetin, 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 class Steroidal antiandrogen; Progestogen; Progestin
Pharmacokinetic data
Bioavailability Oral: Very low (1% in dogs) [5]
Elimination half-life IM Tooltip 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
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H30O2
Molar mass 302.458 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 names Prostetin and Roxenone, is an antiandrogen and progestin medication which is used in Japan in the treatment of enlarged prostate. [7] [8] [9] [10] [11] However, this use is controversial due to concerns about its clinical efficacy. [11] Oxendolone is not effective by mouth and must be given by injection into muscle. [5] [1] [2] [3] [4]

Contents

Oxendolone is an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone. [12] [13] [14] [15] [6] 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. [12] [13] [14] [15] 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. [8] It is used only in Japan. [8] [11]

Medical uses

Oxendolone is used in the treatment of benign prostatic hyperplasia (BPH) in Japan. [8] [11] 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. [11]

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 Tooltip half-maximal inhibitory concentration = 1.4 μM). [12] [13] [14] [15] 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; [13] 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). [7] [8]

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. [8]

Society and culture

Generic names

Oxendolone is the generic name of the drug and its INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name, and JAN Tooltip Japanese Accepted Name. [7] [22] It is also known by its developmental code name TSAA-291. [7] [22]

Brand names

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

Availability

Oxendolone is marketed only in Japan. [22]

Related Research Articles

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Finasteride</span> Antiandrogen medication

Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women. It is usually taken orally but there are topical formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.

<span class="mw-page-title-main">Bicalutamide</span> Prostate cancer treatment

Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration. Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings. Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women, as a puberty blocker and component of feminizing hormone therapy for transgender girls and women, to treat gonadotropin-independent early puberty in boys, and to prevent overly long-lasting erections in men. It is taken by mouth.

<span class="mw-page-title-main">Gestonorone caproate</span> Chemical compound

Gestonorone caproate, also known as gestronol hexanoate or norhydroxyprogesterone caproate and sold under the brand names Depostat and Primostat, is a progestin medication which is used in the treatment of enlarged prostate and cancer of the endometrium. It is given by injection into muscle typically once a week.

<span class="mw-page-title-main">Trestolone</span> Chemical compound

Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and in androgen replacement therapy for low testosterone levels in men but has never been marketed for medical use. It is given as an implant that is placed into fat. As trestolone acetate, an androgen ester and prodrug of trestolone, the medication can also be given by injection into muscle.

<span class="mw-page-title-main">Hydroxyprogesterone caproate</span> Medication

Hydroxyprogesterone caproate, sold under the brand names Proluton and Makena among others, is a medication used to reduce the risk of preterm birth in women pregnant with one baby who have a history of spontaneous preterm birth. In March 2023, the manufacturer, Covis Pharma, agreed to withdraw the drug from the US market. The approvals of Makena and its generics were withdrawn by the US Food and Drug Administration (FDA) in April 2023.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Chlormadinone acetate</span> Chemical compound

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

<span class="mw-page-title-main">Allylestrenol</span> Chemical compound

Allylestrenol, sold under the brand names Gestanin and Turinal among others, is a progestin medication which is used to treat recurrent and threatened miscarriage and to prevent premature labor in pregnant women. However, except in the case of proven progesterone deficiency, its use for such purposes is no longer recommended. It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men. The medication is used alone and is not formulated in combination with an estrogen. It is taken by mouth.

<span class="mw-page-title-main">Estradiol undecylate</span> Chemical compound

Estradiol undecylate, also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen medication which has been used in the treatment of prostate cancer in men. It has also been used as a part of hormone therapy for transgender women. Although estradiol undecylate has been used in the past, it was discontinued and hence is no longer available. The medication has been given by injection into muscle usually once a month.

<span class="mw-page-title-main">Cyproterone acetate</span> Chemical compound

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender women, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

<span class="mw-page-title-main">Cyproterone</span> Chemical compound

Cyproterone, also known by its developmental code name SH-80881, is a steroidal antiandrogen which was studied in the 1960s and 1970s but was never introduced for medical use. It is an analogue of cyproterone acetate (CPA), an antiandrogen, progestin, and antigonadotropin which was introduced instead of cyproterone and is widely used as a medication. Cyproterone and CPA were among the first antiandrogens to be developed.

<span class="mw-page-title-main">Osaterone acetate</span> Chemical compound

Osaterone acetate, sold under the brand name Ypozane, is a medication which is used in veterinary medicine in Europe in the treatment of enlarged prostate in dogs. It is given by mouth.

<span class="mw-page-title-main">Zanoterone</span> Chemical compound

Zanoterone, also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol, is a steroidal antiandrogen which was never marketed. It was investigated for the treatment of benign prostatic hyperplasia (BPH) but failed to demonstrate sufficient efficacy in phase II clinical trials, and also showed an unacceptable incidence rate and severity of side effects. As such, it was not further developed.

<span class="mw-page-title-main">Bifluranol</span> Mixture of two compounds

Bifluranol is a synthetic nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol that has been used as an antiandrogen in the United Kingdom in the treatment of benign prostatic hyperplasia. It is a polyfluorinated biphenyl that is related to polybrominated and polychlorinated biphenyls and diethylstilbestrol. The drug is described as a weak estrogen, and possesses about one-eighth the potency of diethylstilbestrol.

<span class="mw-page-title-main">BOMT</span> Chemical compound

BOMT, also known by its developmental code name Ro 7-2340 and as 6α-bromo-4-oxa-17α-methyl-5α-dihydrotestosterone, is a synthetic steroidal antiandrogen which was first developed in 1970 and was never marketed for medical use. It is the 6α-brominated, 4-oxygenated, and 17α-methylated derivative of the androgen dihydrotestosterone (DHT). Along with benorterone, cyproterone, and flutamide, BOMT was among the earliest antiandrogens to be developed and extensively studied, although it is less well-documented in comparison to the others. BOMT has been investigated clinically in the treatment of benign prostatic hyperplasia, though development for this use did not continue. There was also interest in BOMT for the potential applications of acne, pattern hair loss, and possibly prostate cancer, but it was not developed for these indications either.

<span class="mw-page-title-main">Trimethyltrienolone</span> Chemical compound

Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an antiandrogen medication which was never introduced for medical use but has been used in scientific research.

<span class="mw-page-title-main">Steroidal antiandrogen</span> Class of compounds

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.

<span class="mw-page-title-main">5α-Dihydroethisterone</span> Chemical compound

5α-Dihydroethisterone is an active metabolite of the formerly clinically used but now-discontinued progestin ethisterone and the experimental and never-marketed hormonal antineoplastic agent ethynylandrostanediol (HE-3235). Its formation from its parent drugs is catalyzed by 5α-reductase in tissues that express the enzyme in high amounts like the liver, skin, hair follicles, and prostate gland. 5α-DHET has significant affinity for steroid hormone receptors and may contribute importantly to the activities of its parent drugs.

<span class="mw-page-title-main">Pharmacology of cyproterone acetate</span>

The pharmacology of cyproterone acetate (CPA) concerns the pharmacology of the steroidal antiandrogen and progestin medication cyproterone acetate.

References

  1. 1 2 3 Henkler 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. 1 2 3 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. 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. 1 2 3 Ostri 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. 1 2 3 4 5 Midgley 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. 1 2 3 Iga 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. 1 2 Gao 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. 1 2 3 4 5 Elks 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. 1 2 3 4 5 6 William 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. 1 2 3 4 5 Ishizuka 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. 1 2 3 Mallamo 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. 1 2 3 4 Annual report of Shionogi Research Laboratories. 1991. pp. 76–77.
  14. 1 2 3 Kirby 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. 1 2 3 Bashirelahi 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. 1 2 Sudo 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. 1 2 3 Katayama 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. 1 2 Masuoka 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. 1 2 3 4 "Oxandrolone Uses, Side Effects & Warnings". Drugs.com.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.