Inhibitory effect of α1D/1A antagonist 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide on estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo

Benign prostatic hyperplasia (BPH) is a common disorder of the urinary system in aging men. 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide (HJZ-3), which is derived from naftopidil , exhibited 97.7- and 64.6-fold greater inhibitory effects for a 1D adrenoceptor than for a 1B - and a 1A -adrenoceptors in vitro, respectively. To investigate the therapeutic potential for treating BPH, we evaluated the pharmacological activity of HJZ-3. Specifically, we evaluated through estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo. HJZ-3 effectively prevented the progression of rat prostatic hyperplasia by suppressing the increase in prostate index and reducing the quantitative analysis of the relative acinus volume, relative stroma, epithelial volume and epithelial thickness and expression of proliferating cell nuclear antigen and α -smooth muscle actin. HJZ-3 decreased α 1A - and α 1D -adrenoceptor protein expressions in prostate tissue. HJZ-3 is a good alternative for α 1A - and α 1D -adrenoceptor blocker. It may relax smooth muscle tone and relieve symptoms of BPH.