Pharmacological properties of Z-350, which possesses α_1 -adrenoce ptor antagonistic and steroid 5α-reductase inhibitory actions

• Published in: Japanese Journal of Pharmacology 1998, Vol.76 (suppl.2), p.242-242
• Main Authors: Yoshihisa Fukuta, Youichi Fukuda, Raita Higashino, Kenji Yoshida, Masayuki Ogishima, Shigeru Furuta, Emiko Kamata, Haruka Miyahara, Mineo Takei, Tadashi Kurimoto, Yoshiaki Tanaka, Hajime Tamaki
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Z-350 ((S)-4-{3-{4-{1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy}benzoyl}indole-1-yl) butyric acid hydrochloride) is a newly synthesized compound which has α_1 -antagonistic and steroid 5α-reductase inhibitory actions. In the present study, we investigated pharmacological properties of Z-350 in vivo. Z-350 (1-10 mg/kg, i.d.) dose-dependently inhibited phenylephrine-induced increases of urethral pressure (⊿UP) in anesthetized male rabbits, whereas the effects for mean blood pressure and orthostatic hypotension were weaker than the effect on ⊿UP in the tested dose range. Z-350 (p.o.) inhibited prostatic steroid 5α-reductase activity with ED_50 of 2.81 mg/kg in rats, and its dose- and time-dependent inhibitory actions were well matched with the concentration of Z-350 in prostatic tissue. In addition, testosterone-induced prostatic growth in castrated rats was reduced by Z-350 (3-30 mg/kg, p.o.). These results indicate that Z-350 reveals α_1 -antagonistic and steroid 5α-reductase inhibitory actions in the similardose range, suggesting that such dual actions of the compound may contribute to the treatment of benign prostatic hyperplasia.