Leuprolide acetate: a drug of diverse clinical applications

Abstract

Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide acetate suppresses gonadotrope secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses gonadal sex steroid production. In addition, leuprolide acetate is presently being tested for the treatment of Alzheimer's disease, polycystic ovary syndrome, functional bowel disease, short stature, premenstrual syndrome and even as an alternative for contraception. Mounting evidence suggests that GnRH agonist suppression of serum gonadotropins may also be important in many of the clinical applications described above. Moreover, the presence of GnRHR in a multitude of non-reproductive tissues including the recent discovery of GnRHR expression in the hippocampi and cortex of the human brain indicates that GnRH analogs such as leuprolide acetate may also act directly via tissue GnRHRs to modulate (brain) function. Thus, the molecular mechanisms underlying the therapeutic effect of GnRH analogs in the treatment of these diseases may be more complex than originally thought. These observations also suggest that the potential uses of GnRH analogs in the modulation of GnRH signaling and treatment of disease has yet to be fully realized.

Urinary Metabolite Markers of Precocious Puberty

“…Correct diagnosis of the etiology of sexual precocity is critical, because treatment of patients with PPP is different from those with CPP, and some PPP can secondarily evolve into CPP (6). Standard treatment of CPP is to suppress the activation of HPGA (7) through periodically using GnRH agonists such as leuprorelin depot (8) and triptorelin depot (9,10). Patients with CPP have to continue receiving this medication until they reach the average age of the onset of puberty.…”

Interface Peptide Mimetics-Rationale and Application as Therapeutic Agents

“…Additionally, amino terminal acetylation presumably increases the peptide lipophilicity enhancing the membrane permeability and passage across the intestinal or blood brain barrier [8,16,19]. An acetate salt of a peptide analog of the gonadotropin releasing hormone (GnRH) acts as a potent inhibitor of gonadotropin secretion and has diverse clinical applications [20].…”

Liquid Chromatographic Estimation of Leuprolide Acetate in Bulk and Microsphere Formulation

“…It is also used to treat hormonal related mammary cancer, endometriosis and precocious puberty. It is analogue of luteinizing hormone so it increases gonadotropin hormone secretion by pituitary and steroidogenesis, but at higher doses, contradictly produces antagonist effect on pituitary and inhibit gonadotropin secretion which results in temporary or reversible down regulation of receptors [1]. Leuprolide acetate is chemically N-ethyl-1-[(5-oxopyrrolidone-2-carbonyl)histidyl tryptophyl seryl tyrosyl leucyl leucyl arginglyl]pyrrolidone-2-carboxamide and the structure of molecule is shown in Fig.…”