Hairloss Study Abstract: Endocrine profile of Win 49596 in the rat: a novel androgen receptor antagonist.

Title: Endocrine profile of Win 49596 in the rat: a novel androgen receptor antagonist.
Title Abreviation: J Steroid Biochem		Date of Pub: 1989 Dec
Author: Snyder BW; Winneker RC; Batzold FH;
Issue/Part/Supplement: 6	Volume Issue: 33		Pagination: 1127-32
MESH Headings: Anilides (PD); Animal; Estrogen Antagonists (PD); Female; Flutamide (PD); Genitalia, Male (DE); Male; Orchiectomy; Pregnanes (PD); Progesterone (AI); Pyrazoles (PD); Rabbits; Rats; Rats, Inbred Strains; Receptors, Androgen (*AI); Testosterone (BL); -RN-;
Journal Title Code: K70	Publication Type: JOURNAL ARTICLE
Date of Entry: 900227N	Entry Month: 9005
Country: ENGLAND	Index Priority: 2
Language: Eng	Unique Identifier: 90135091
Unique Identifier: 90135091	ISSN: 0022-4731
Abstract: 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.
Abstract By: Author
Address: Department of Pharmacology, Sterling Research Group, Rensselaer, NY 12144.