Effects of a new non-steroidal 5 alpha-reductase inhibitor, FK143, on the prostate gland in beagle dogs.
FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl] - butyric acid) is a new non-steroidal inhibitor of steroid 5 alpha-reductase (5 alpha-reductase). The effects of FK143 on prostate size and histopathology of mature male beagle dogs were investigated and compared with those of finasteride (a steroidal 5 alpha-reductase inhibitor), and allylestrenol and chlormadinone acetate (CMA) (androgen receptor antagonists). FK143 was orally administered to the dogs daily for 12 weeks. At doses of 10 and 32 mg/kg, FK143 significantly reduced prostate volume to about 60% of the initial value, and dogs treated with FK143 showed a dose-dependent glandular epithelial atrophy in the prostate. FK143 showed no abnormal changes in organ weights and histopathology of the adrenal, testis, pituitary and liver. The degree of prostate reduction in the dogs treated with FK143 (10 and 32 mg/kg) was almost the same as that by finasteride (1.0 mg/kg) and smaller than that by allylestrenol (10 mg/kg) or CMA (10 mg/kg). However, allylestrenol increased liver weights, and CMA increased liver and reduced adrenal weights. These results demonstrate that FK143 can decrease the volume of the dog prostate without any influence on other organs, and they suggest that FK143 is a good candidate for the treatment for benign prostatic hyperplasia.
Inami
M
M
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Kawamura
I
I
Naoe
Y
Y
Tsujimoto
S
S
Mizota
T
T
Manda
T
T
Shimomura
K
K
D058891:5-alpha Reductase Inhibitors; D000500:Allylestrenol / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000818:Animals; D002715:Chlormadinone Acetate / Q000494:pharmacology; D004285:Dogs; D018120:Finasteride / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology; D011467:Prostate / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism; D014463:Ultrasonography
C093354:4-(3-(3-(bis(4-isobutylphenyl)methylamino)benzoyl)-1H-indol-1-yl)butyric acid; D058891:5-alpha Reductase Inhibitors; D059002:Androgen Receptor Antagonists; D007211:Indoles; D010654:Phenylbutyrates; D045167:Progesterone Congeners; D011944:Receptors, Androgen; D002715:Chlormadinone Acetate; D018120:Finasteride; D000500:Allylestrenol