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Acetate : A Synthetic Nonapeptide And Analogue Of Naturally Occurring Luteinizing Hormone Releasing Hormone

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Leuprolide Acetate

Leuprolide acetate is a synthetic nonapeptide and analogue of naturally occurring luteinizing hormone releasing hormone (LHRH). It possesses greater biological potency than the natural hormone, which when introduced into the systemic circulation induces the release of luteinizing (LH) and follicle stimulating hormone (FSH) from the anterior pituitary (Schally et al., 1971). It is the blood-borne messenger between the hypothalamus and the anterior pituitary, which controls reproductive function. LHRH is a decapeptide hormone (pGlu-His-Trp-Ser-Tyr-GlyLeu-Arg-Pro-Gly-NH,), which is synthesized and stored in the hypothalamus in neurons which project to the median eminence. LHRH is released in periodic bursts into the hypophyseal portal circulation, where it induces the release of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) into the systemic circulation. These factors then produce a trophic and steroidogenic effect upon the gonadal tissues (Rippel et al., 1974; Johnson et al., 1976).

Rough work
Presently, leuprolide is administered by parenteral routes: 11.25- and 22.5-mg, 3-month depot intramuscular injection (Lupron Depot®) and 1-mg daily subcutaneous injection (Lupron®).

The discovery of the releasing hormone brought about the success in the development of highly synthesised potent analogs (Karten et al., 1986)

Chemistry

Leuprolide acetate has three ionizable sites, namely the imidazolyl nitrogen of histidine (pK,

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