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| 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. |
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