Win 49596 is a new orally active, steroidal
androgen receptor antagonist.
Win 49596 inhibited ventral prostate, seminal vesicle and levator ani
weight gain in either
5 alpha-dihydrotestosterone (DHT) or
testosterone propionate-treated castrated, immature male rats. In intact, adult male rats,
Win 49596 significantly inhibited
weight gain by the ventral prostate, dorsal lateral prostate and seminal vesicles, but not the testes at doses as low as 50 mg/kg/day x 14 p.o. However, daily
oral administration of equivalent antiandrogenic doses of either
Win 49596, ICI 176,334, or
flutamide for 14 days to mature, intact male rats resulted in elevations of circulating
testosterone of approximately 3-, 2-, and 10-fold, respectively. At doses as high as 400 mg/kg p.o.,
Win 49596 did not have androgenic, progestational, estrogenic or antiestrogenic activity in rat or rabbit models. However, in the Clauberg assay,
Win 49596 did have weak antiprogestational activity at doses of 25-400 mg/kg/day p.o. These data indicate that
Win 49596 is a peripherally selective
antiandrogen that has minimal effects on circulating
testosterone levels and is devoid of
hormone agonist activity. Thus,
Win 49596 may be useful for the treatment of
androgen dependent conditions such as
benign prostatic hyperplasia and
prostatic cancer.