Effect of the steroidal androgen receptor antagonist Win 49,596 on steroid-induced benign prostatic hyperplasia in the castrate beagle dog.
The effects of the steroidal androgen receptor antagonist Win 49,596 on steroid-induced prostatic growth, histomorphology, and secretory function were studied in the castrate male beagle dog. At oral doses ranging from 0.625 to 40 mg/kg/day for 12 weeks, Win 49,596 inhibited prostatic growth in terms of both weight and total DNA in a dose-dependent manner. In addition, both the incidence and severity of diffuse glandular hyperplasia/hypertrophy were dose-dependently inhibited by Win 49,596, resulting in diffuse glandular atrophy. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at a dosage of 40 mg/kg/day were similar to that observed for the nonsteroidal androgen receptor antagonist flutamide at 10 mg/kg/day. Oral administration of Win 49,596 to castrate dogs at a dosage of 40 mg/kg/day for 12 weeks failed to produce any evidence of agonist activity. These results demonstrate that Win 49,596 prevented the experimental induction of benign prostatic hyperplasia in dogs and suggest that on further evaluation this compound may be efficacious in the treatment of the human disease.
Juniewicz
P E
PE
Department of Pharmacology, Sterling Research Group, Rensselaer, New York 12144.
Lemp
B M
BM
Barbolt
T A
TA
LaBrie
T K
TK
McCarthy
M
M
Reel
J R
JR
Batzold
F H
FH
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000097:blood; D000818:Animals; D004247:DNA / Q000032:analysis; D004285:Dogs; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011278:Pregnanes / Q000494:pharmacology* / Q000627:therapeutic use; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014463:Ultrasonography
D000726:Androgen Antagonists; D000728:Androgens; D011278:Pregnanes; D011720:Pyrazoles; D004247:DNA; C060492:zanoterone