TY - JOUR T1 - Z-350, A Novel Compound with α<sub>1</sub>-Adrenoceptor Antagonistic and Steroid 5α-Reductase Inhibitory Actions: Pharmacological Properties In Vivo JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1013 LP - 1018 VL - 290 IS - 3 AU - Yoshihisa Fukuta AU - Youichi Fukuda AU - Raita Higashino AU - Kenji Yoshida AU - Masayuki Ogishima AU - Hajime Tamaki AU - Mineo Takei Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/1013.abstract N2 - The α1-adrenoceptor-antagonistic and steroid 5α–reductase-inhibitory actions 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] were investigated in rabbits and rats in vivo. Z-350 (1–30 mg/kg), administered intraduodenally, dose-dependently inhibited phenylephrine-induced increases in prostatic urethral pressure with an ED50 value of 3.8 mg/kg in anesthetized male rabbits, whereas the effects on mean blood pressure and orthostatic hypotensive response were weaker when compared with other α1-adrenoceptor antagonists, tamsulosin and prazosin. Z-350 (1–10 mg/kg p.o.) dose-dependently inhibited the prostatic steroid 5α-reductase activity in rats with an ED50 value of 2.8 mg/kg. The daily oral administration of Z-350, at ≧10 mg/kg for 7 days, significantly reduced the prostatic growth induced by testosterone in castrated rats, with no effect on dihydrotestosterone-induced prostatic growth. These results indicate that Z-350 exhibited α1-adrenoceptor-antagonistic and 5α-reductase inhibitory actions at almost equal doses in vivo, and was expected to improve the bladder outlet obstruction associated with benign prostatic hyperplasia with smaller cardiovascular adverse effect. The American Society for Pharmacology and Experimental Therapeutics ER -