Hormonal Effects of Z-350, Possessing Steroid 5α-Reductase Inhibitory and α₁-Adrenoceptor Antagonistic Actions, in the Rat

Abstract

We examined the hormonal effects of Z-350, (S)-4-[3-(4-{1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy}benzoyl)indole-1-yl]butyric acid hydrochloride, which has both α₁-adrenoceptor blocking activity and steroid 5α-reductase inhibitory activity, in male and female rats. Z-350 administered orally for 14 days at a dose of 30 mg/kg to normal male rats significantly reduced the weight of the prostate and seminal vesicles without affecting the weight of the testis, epididymis, adrenals, kidney or liver. Prostatic levels of dihydrotestosterone decreased dose-dependently, with a slight increase in the level of testosterone at a Z-350 dose of 100 mg/kg. We observed no effects on the weight of the prostate in castrated rats or on the weight of the uterus in normal or 17β-estradiol-treated female rats. These results suggest that Z-350 inhibits prostatic growth via inhibition of steroid 5-reductase without other hormonal effects.