Jpn. J. Pharmacol. 74 (2), 187-194 (1997)
Effects of a New Non-Steroidal 5alpha-Reductase Inhibitor, FK143, on
the Prostate Gland in Beagle Dogs
Masamichi Inami, Ikuo Kawamura, Yoshinori Naoe, Susumu Tsujimoto, Tamotsu
Mizota, Toshitaka Manda and Kyoichi Shimomura
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
2-1-6, Kashima, Yodogawa-ku, Osaka 532, Japan
Abstract: FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl]-butyric
acid) is a new non-steroidal inhibitor of steroid 5alpha-reductase (5alpha-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 5alpha-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.
Keywords: FK143, 5alpha-Reductase, Benign prostatic hyperplasia
Copyright© The Japanese Pharmacological Society 1997
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