Histrelin

Histrelin

Systematic (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
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a601146
Pregnancy category	US: X (Contraindicated)
Legal status	US: ℞-only
Routes of administration	Subcutaneous implant
Pharmacokinetic data
Bioavailability	92%
Protein binding	70%
Metabolism	Hepatic
Biological half-life	4.0 hours
Excretion	Undetermined
Identifiers
CAS Number	76712-82-8 N
ATC code	L02AE05 (WHO)
PubChem	CID: 25077993
IUPHAR/BPS	3884
ChemSpider	10482012 Y
UNII	H50H3S3W74 Y
KEGG	D02369 Y
ChEMBL	CHEMBL1201255 N
Chemical data
Formula	C66H86N18O12
Molecular mass	1323.5 g/mol
SMILES CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(C=N2)CC3=CC=CC=C3)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CC7=CNC=N7)NC(=O)[C@@H]8CCC(=O)N8
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 is a nonapeptide analog 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.

Histrelin is marketed by Endo Pharmaceuticals under the brand names Vantas and Supprelin LA.

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 is also part of the primary care protocol in transgender children/youth, and is used in suppressing cis-sex puberty, until the patient is ready to begin cross-sex hormonal therapy.

Adverse effects

Side effects are mainly due to low testosterone levels and include headache, hot flashes, reduced libido, 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 LH and 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.

External links

• Central Precocious Puberty