Triptorelin

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).^[3][4]

Triptorelin

Clinical data
Trade names	Decapeptyl, others
AHFS/Drugs.com	Micromedex Detailed Consumer Information
License data	US DailyMed: Triptorelin
Routes of administration	Intramuscular
Drug class	GnRH analogue; GnRH agonist; Antigonadotropin
ATC code	L02AE04 (WHO) QH01CA97 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[1] CA: ℞-only US: ℞-only[2] In general: ℞ (Prescription only)
Pharmacokinetic data
Excretion	Kidney
Identifiers
IUPAC name 5-oxo-D-prolyl-L-histidyl-Ltryptophyl-L-seryl-Ltyrosyl-3-(1H-indol-2-yl)-L-alanylleucyl-L-arginyl-L-prolylglycinamide
CAS Number	57773-63-4 N
PubChem CID	25074470
IUPHAR/BPS	1177
DrugBank	DB06825 N
ChemSpider	17290424 N
UNII	9081Y98W2V
KEGG	D06247 N D08649
ChEBI	CHEBI:63633 N
ChEMBL	ChEMBL1201334 N
CompTox Dashboard (EPA)	DTXSID2048375
ECHA InfoCard	100.165.044
Chemical and physical data
Formula	C64H82N18O13
Molar mass	1311.473 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N)NC(=O)[C@@H](Cc2c[nH]c3c2cccc3)NC(=O)[C@H](Cc4ccc(cc4)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc5c[nH]c6c5cccc6)NC(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@@H]8CCC(=O)N8
InChI InChI=1S/C64H82N18O13/c1-34(2)23-46(56(88)75-45(13-7-21-69-64(66)67)63(95)82-22-8-14-52(82)62(94)72-31-53(65)85)76-58(90)48(25-36-28-70-42-11-5-3-9-40(36)42)78-57(89)47(24-35-15-17-39(84)18-16-35)77-61(93)51(32-83)81-59(91)49(26-37-29-71-43-12-6-4-10-41(37)43)79-60(92)50(27-38-30-68-33-73-38)80-55(87)44-19-20-54(86)74-44/h3-6,9-12,15-18,28-30,33-34,44-52,70-71,83-84H,7-8,13-14,19-27,31-32H2,1-2H3,(H2,65,85)(H,68,73)(H,72,94)(H,74,86)(H,75,88)(H,76,90)(H,77,93)(H,78,89)(H,79,92)(H,80,87)(H,81,91)(H4,66,67,69)/t44-,45-,46-,47-,48+,49-,50-,51-,52-/m0/s1 N Key:VXKHXGOKWPXYNA-PGBVPBMZSA-N N
NY (what is this?)  (verify)

It is a decapeptide (pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH₂) and a gonadotropin-releasing hormone agonist (GnRH agonist) used as the acetate or pamoate salts.

Primary indications include endometriosis,^[5] for the reduction of uterine fibroids, to treat prostate cancer, and to treat male hypersexuality with severe sexual deviation.^[4] The drug has also been used off label to delay puberty in patients with gender dysphoria.^[6]

It was patented in 1975 and approved for medical use in 1986.^[7] It is on the World Health Organization's List of Essential Medicines.^[8]

Medical uses

See also: Gonadotropin-releasing hormone agonist § Medical uses

Triptorelin is used to treat prostate cancer as part of androgen deprivation therapy.^[9]

Another common use in the United Kingdom is for hormone replacement therapy to suppress testosterone or estrogen levels in transgender people (in conjunction with estradiol valerate for trans women or testosterone for trans men). Spironolactone and cyproterone acetate are other drugs used by trans people to suppress sex hormones, but these drugs have a completely different mechanism of action.^[10] It can also be used as a puberty blocker^[11] in the case of precocious puberty.^[9]

Triptorelin has been used as a chemical castration agent for reducing sexual urges in sex offenders.^[12]

Drug action

Triptorelin is a gonadorelin analogue, also known as luteinizing hormone releasing analogue (GnRH analogue, LHRH analogue).^[3] The drug binds to receptors in the pituitary gland and stimulates secretion of gonadotropins (namely luteinizing hormone LH and follicle-stimulating hormone FSH). This causes an initial phase of LH and FSH stimulation, prior to down-regulation of the gonadotrophin-releasing hormone receptors, thereby reducing the release of gonadotropins in the long term, which in turn leads to the inhibition of androgen and estrogen production.^[4]

Side-effects

General side effects can include:^[4]

• Anaphylaxis
• Arthralgia
• Asthenia
• Asthma
• Breast tenderness (males and females)
• Changes in blood pressure
• Changes in breast size
• Depression
• Ovarian cysts
• Mood changes
• Skin rashes
• Hot flushes
• Weight changes

Society and culture

Brand names

Triptorelin is marketed under the brand names Decapeptyl (Ipsen) for treating prostate cancer, endometriosis, uterine myomas, and precocious puberty,^[13] and Diphereline and Gonapeptyl (Ferring Pharmaceuticals).^[14] In the United States, it is sold by Watson Pharmaceuticals as Trelstar ^[15] and by Arbor Pharmaceuticals as Triptodur (an extended-release 6-month depot injection).^[16] In Iran, triptorelin is marketed under the brand name Variopeptyl. In the UK and Germany, it is sold as Salvacyl for the treatment of sexual deviations.^[17]

History

Triptorelin was developed in Andrew V. Schally's lab at Tulane University.^[18] Debiopharm licensed the drug from Tulane in 1982.^[19]

Research

Triptorelin and other antiandrogens may be effective in the treatment of obsessive–compulsive disorder.^[20]

References

1. "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
2. "Triptodur- triptorelin kit". DailyMed. U.S. National Library of Medicine. 28 April 2022. Retrieved 15 May 2022.
3. "gonadorelin analogue". Encyclopedia.com. Retrieved 2019-09-21.
4. Joint Formulary Committee (2018). British National Formulary (BNF) 70. London: Pharmaceutical Press. p. 635. ISBN 978-0-85711-173-9.
5. Leone Roberti Maggiore U, Scala C, Remorgida V, Venturini PL, Del Deo F, Torella M, et al. (June 2014). "Triptorelin for the treatment of endometriosis". Expert Opinion on Pharmacotherapy. 15 (8). Informa Healthcare: 1153–1179. doi:10.1517/14656566.2014.916279. PMID 24832495. S2CID 23843087.
6. Cohen D, Barnes H (September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ. 366: l5647. doi:10.1136/bmj.l5647. PMID 31540909. S2CID 202711942.
7. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN 9783527607495.
8. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
9. "triptorelin (Intramuscular route)". Drugs.com. Retrieved 11 November 2016.
10. Wylie KR, Fung Jr R, Boshier C, Rotchell M (2009). "Recommendations of endocrine treatment for patients with gender dysphoria". Sexual and Relationship Therapy. 24 (2): 175–187. doi:10.1080/14681990903023306. S2CID 20471537.
11. Shumer DE, Nokoff NJ, Spack NP (August 2016). "Advances in the Care of Transgender Children and Adolescents". Advances in Pediatrics. 63 (1): 79–102. doi:10.1016/j.yapd.2016.04.018. PMC 4955762. PMID 27426896.
12. "Study: Drug effectively treats pedophilia". CNN. 11 February 1998.
13. "Decapeptyl SR 11.25mg (triptorelin pamoate) - Patient Information Leaflet (PIL) - (emc)". www.medicines.org.uk. Retrieved 2022-11-14.
14. "Gonapeptyl Depot 3.75 mg - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Retrieved 2022-11-14.
15. "Trelstar intramuscular: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing". WebMD. Retrieved 2022-11-14.
16. "Triptodur Intramuscular: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing". WebMD. Retrieved 2022-11-14.
17. "Salvacyl®, developed by Debiopharm, is launched in two European countries - a new therapeutic avenue for the treatment of sexual deviations". Debiopharm. 23 June 2009. Retrieved 2022-11-14.
18. "About Us – Technology Transfer at Tulane University". Tulane University. Retrieved 4 January 2024.
19. "Dr. Reddy's Launches Debiopharm's Pamorelin LA in India for the Treatment of Locally Advanced or Metastatic, Hormone-Dependent Prostate Cancer". Fierce Pharma. 7 December 2012. Retrieved 4 January 2024.
20. Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A (December 2019). "Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review". Current Medicinal Chemistry. 27 (40): 6825–6836. doi:10.2174/0929867326666191209142209. PMID 31814547. S2CID 208956450.

Further reading

• Lahlou N, Carel JC, Chaussain JL, Roger M (July 2000). "Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics". Journal of Pediatric Endocrinology & Metabolism. 13 (Suppl 1): 723–737. doi:10.1515/jpem.2000.13.s1.723. PMID 10969915. S2CID 3639804.
• Padula AM (August 2005). "GnRH analogues--agonists and antagonists". Animal Reproduction Science. 88 (1–2): 115–126. doi:10.1016/j.anireprosci.2005.05.005. PMID 15955640.

External links

• "Triptorelin". Drug Information Portal. U.S. National Library of Medicine.