Hence, it is described as nonsteroidal in order to distinguish it from older steroidal antiandrogens such as cyproterone acetate and megestrol acetate. Synthesis
History
Flutamide was first synthesized in 1967 by Neri and colleagues at Schering Plough Corporation. It was originally synthesized as a bacteriostatic agent, but was subsequently, and serendipitously found to possess antiandrogen activity. The code name of flutamide during development was SCH-13521. Clinical research of the medication began in 1971, and it was first marketed in 1983, specifically in Chile under the brand name Drogenil and in West Germany under the brand name Flugerel. Flutamide was not introduced in the United States until 1989; it was specifically approved by the U.S. Food and Drug Administration for the treatment of metastatic prostate cancer in combination with a gonadotropin-releasing hormone (GnRH) analogue. The medication was first studied for the treatment of hirsutism in women in 1989. It was the first "pure antiandrogen" to be studied in the treatment of hirsutism. Flutamide was the first NSAA to be introduced, and was followed by nilutamide in 1989 and then bicalutamide in 1995. Society and culture
Generic names
Flutamide is the generic name of the drug and its INN, USAN, BAN, DCF, and JAN. Its names in Latin, German, and Spanish are flutamidum, flutamid, and flutamida, respectively. The medication has also been referred to by the name niftolide. Brand names
Brand names of flutamide include or have included Cebatrol, Cytomid, Drogenil, Etaconil, Eulexin, Flucinom, Flumid, Flutacan, Flutamid, Flutamida, Flutamin, Flutan, Flutaplex, Flutasin, Fugerel, Profamid, and Sebatrol, among others.
A variety of case reports have associated flutamide with photosensitivity. Flutamide has been associated with several case reports of methemoglobinemia. Bicalutamide does not appear to share this risk with flutamide. Flutamide has also been associated with reports of sulfhemoglobinemia and neutropenia. Birth defects
Out of the available endocrine-disrupting compounds looked at, flutamide has a notable effect on anogenital distance in rats.) Pharmacology
Pharmacodynamics
Antiandrogenic activity
Flutamide acts as a selective, competitive, silent antagonist of the androgen receptor (AR). Its active form, hydroxyflutamide, has between 10- to 25-fold higher affinity for the AR than does flutamide, and hence is a much more potent AR antagonist in comparison. However, at high concentrations, unlike flutamide, hydroxyflutamide is able to weakly activate the AR. Flutamide has far lower affinity for the AR than do steroidal antiandrogens like spironolactone and cyproterone acetate, and it is a relatively weak antiandrogen in terms of potency by weight, but the large dosages at which flutamide is used appear to compensate for this. In accordance with its selectivity for the AR, flutamide does not interact with the progesterone, estrogen, glucocorticoid, or mineralocorticoid receptor, and possesses no intrinsic progestogenic, estrogenic, glucocorticoid, or antigonadotropic activity. However, it can have some indirect estrogenic effects via increased levels of estradiol secondary to AR blockade, and this involved in the gynecomastia it can produce. Because flutamide does not have any estrogenic, progestogenic, or antigonadotropic activity, the medication does not cause menstrual irregularities in women. This is in contrast to steroidal antiandrogens like spironolactone and cyproterone acetate.