Overdose
Interactions
Pharmacology
Pharmacodynamics
Norgestimate is a rapidly and completely converted prodrug, mainly of norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), but also of levonorgestrel (3-keto-17β-deacetylnorgestimate) to a lesser extent (22 ± 6% of an administered dose or about 40–70 µg) and of levonorgestrel acetate (levonorgestrel 17β-acetate) in very small amounts. Via its active metabolites, norgestimate has progestogenic activity, antigonadotropic effects, very weak androgenic activity, and no other important hormonal activity. Progestogenic activity
Norgestimate is a progestogen, or an agonist of the progesterone receptor. The relative binding affinities of norgestimate and its active metabolites for the progesterone receptor compared to promegestone (100%) are 15% for norgestimate, 10% for norelgestromin, 150% for levonorgestrel, and 135% for levonorgestrel acetate. Because of their low concentrations, norgestimate and levonorgestrel acetate are not thought to contribute significantly to the biological activity of norgestimate. In addition, although levonorgestrel binds to the progesterone receptor with much higher affinity than norelgestromin, levonorgestrel has high affinity for sex hormone-binding globulin (SHBG) (87% of that of testosterone), which may limit its activity, whereas norelgestromin does not bind to SHBG. The ovulation-inhibiting dosage of norgestimate is 200 µg/day. Androgenic activity
In addition to its progestogenic activity, norgestimate has weak androgenic activity. However, the medication shows less androgenic activity than related 19-nortestosterone progestins like levonorgestrel and norethisterone. Norgestimate and norelgestromin have negligible affinity for the androgen receptor (both 0% of the affinity of metribolone), while levonorgestrel has considerable affinity for the androgen receptor (45% of that of metribolone).
Unlike the combined birth control pills of norgestimate with ethinylestradiol, the combination of norgestimate with estradiol, sold under the brand name Prefest for menopausal hormone therapy, is reportedly only marketed currently in the United States and Brazil. Research
A 2017 study found that norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to β-lactam antibiotics. In contrast, norelgestromin showed much weaker activity, indicating that the acetyl group of norgestimate is important for the activity. It was suggested by the researchers that norgestimate may be a promising lead compound for the development of new antibiotics. References
Further reading
Henzl MR (July 2001). "Norgestimate. From the laboratory to three clinical indications". J Reprod Med. 46 (7): 647–61. PMID 11499185. Curran MP, Wagstaff AJ (2001). "Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women". Drugs Aging. 18 (11): 863–85. doi:10.2165/00002512-200118110-00007. PMID 11772126. S2CID 22720686. Curran MP, Wagstaff AJ (2002). "Spotlight on estradiol and norgestimate as hormone replacement therapy in postmenopausal women". Treat Endocrinol. 1 (2): 127–9. doi:10.2165/00024677-200201020-00006. PMID 15765628. S2CID 1936039. External links
"Norgestimate". Drug Information Portal. U.S. National Library of Medicine. "Ethinyl estradiol mixture with norgestimate". Drug Information Portal. U.S. National Library of Medicine. "Estradiol mixture with norgestimate". Drug Information Portal. U.S. National Library of Medicine.