| Pharmaceutical Application: |
Buserelin |
| Applications: |
The product may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), and in assisted reproduction. |
| Examples of Clinical Use: |
Hormone-responsive cancers |
| Pharmacodynamics: |
The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects on FSH and LH release are 20 to 170 times greater than those of LHRH. The product also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours.Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50-500 mcg SC/day or 300-1200 mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis. |
| Mechanism of action: |
Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones. |
| Affected organisms: |
Humans and other mammals |
| Targets: |
Target 1. Lutropin-choriogonadotropic hormone receptor; Target 2. Gonadotropin-releasing hormone receptor; Enzyme 1. Cytochrome P450 19A1 |
