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 Histrelin Acetate

Supprelin LA (histrelin acetate) subcutaneous implant contains a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH) that possesses a greater potency than the natural sequence hormone. The chemical name of histrelin acetate is:  L-Pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-N-benzyl-D-histidyl-L-leucyl-L-arginyl-L-proline Nethylamide, acetate salt. The molecular formula for histrelin acetate is C66H86N18O12 x 2 CH3COOH and its molecular weight is 1443.70 (or 1323.52 as free base). Histrelin is also chemically described as 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-Lseryl- L-tyrosyl-Nt-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide diacetate.

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. 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. See http://en.wikipedia.org/wiki/Histrelin.

Mechanism of Action

Supprelin LA is a GnRH agonist and an inhibitor of gonadotropin secretion when given continuously. It delivers approximately 65 mcg histrelin acetate per day. Both animal and human studies indicate that following an initial stimulatory phase, chronic, subcutaneous administration of histrelin acetate desensitizes responsiveness of the pituitary gonadotropin which, in turn causes a reduction in ovarian and testicular steroidogenesis.
In humans, administration of histrelin acetate results in an initial increase in circulating levels of LH and FSH, leading to a transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of histrelin acetate causes a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. These inhibitory effects result in decreased levels of LH and FSH.

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