Chemistry:Histrelin

Short description: Chemical compound

Histrelin

Clinical data
Trade names	Vantas, Supprelin LA, others
AHFS/Drugs.com	Monograph
MedlinePlus	a601146
Pregnancy category	US: X (Contraindicated)
Routes of administration	Subcutaneous implant
Drug class	GnRH analogue; GnRH agonist; Antigonadotropin
ATC code	L02AE05 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	92%
Protein binding	70%
Metabolism	Hepatic
Elimination half-life	4.0 hours
Identifiers
IUPAC name 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-N5-(diaminomethylene)-L-ornithyl-N-ethyl-L-prolinamide
CAS Number	76712-82-8 N
PubChem CID	25077993
IUPHAR/BPS	3884
ChemSpider	10482012 Y
UNII	H50H3S3W74
KEGG	D02369 Y
ChEMBL	ChEMBL1201255 N
Chemical and physical data
Formula	C66H86N18O12
Molar mass	1323.528 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc1cn(Cc2ccccc2)cn1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
InChI InChI=1S/C66H86N18O12/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71)/t47-,48-,49-,50-,51-,52-,53+,54-,55-/m0/s1 Y Key:HHXHVIJIIXKSOE-QILQGKCVSA-N Y
NY (what is this?)  (verify)

Histrelin acetate, sold under the brand names Vantas and Supprelin LA among others, is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency. When present in the bloodstream, it acts on particular cells of the pituitary gland called gonadotropes. Histrelin stimulates these cells to release luteinizing hormone and follicle-stimulating hormone. Thus it is considered a gonadotropin-releasing hormone agonist or GnRH agonist.

Medical uses

Histrelin is used to treat hormone-sensitive cancers of the prostate in men and uterine fibroids in women. In addition, histrelin has been proven to be highly effective in treating central precocious puberty in children.

It is available as a daily intramuscular injection.

Histrelin is also available in a 12-month subcutaneous implant (Vantas) for the palliative treatment of advanced prostate cancer, since 2005 in the US, and since Jan 2010 in the UK.

A 12-month subcutaneous implant (Supprelin LA) for central precocious puberty (CPP) was approved on May 3, 2007 by the U.S. Food and Drug Administration.

Histrelin can be part of the primary care protocol in transgender children/youth, which is an off-label use in the USA and the UK, and is used in suppressing cis-sex puberty, until the patient is ready to begin cross-sex hormonal therapy. It is also sometimes prescribed to transgender adults who benefit from having their sex hormone production halted. In this application, patients often keep the implant for two years before replacing, with regular blood tests to monitor the hormone levels. Implants left too long are more difficult to replace.

Since 2020, Vantas is not available anymore. Endo, its manufacturer said batches of the medication were not coming out right. They added that although Supprelin and Vantas were manufactured in the same facility, they were not identical product (though both contain 50 mg of histrelin acetate.) As of 2023, Vantas is still not available and the only available implant is Supprelin LA.

Vantas was priced around $4400 in 2004 while Supprelin LA was priced at $37,000 in 2007.

Side effects

Common side effects include headache, hot flashes, constipation, reduced libido, gynecomastia, insomnia, renal impairment, weight loss, testicular atrophy, and erectile dysfunction.

Pharmacology

In a process known as downregulation, daily stimulation of pituitary gonadotropes causes them to become desensitized to the effects of histrelin. As a consequence, levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) fall after a short period of time. From that point forward, as long as histrelin is administered, the levels of LH and FSH in the blood remain low.

This prolonged lowering of LH and FSH levels is the rationale for therapy using GnRH agonists. Since LH and FSH stimulate the gonads to produce estrogens and androgens in females and males respectively, histrelin can effectively be used to decrease the sex steroids in the blood of patients.

See also

• Gonadotropin-releasing hormone receptor § Agonists

External links

• "Central Precocious Puberty". Endo Pharmaceuticals. June 2009. http://www.supprelinla.com/aboutcpp/index.html.