Pharmaceutical evaluation of naftopidil enantiomers: Rat functional assays in vitro and estrogen/androgen induced rat benign prostatic hyperplasia model in vivo

Abstract Naftopidil (NAF) is a α 1D/1A adrenoceptor selective drug used for the treatment of both benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS). However, NAF is used as a racemate in clinic. To compare the differences and similarities among two enantiomers and racemate, pharmacological activities were evaluated through rat functional assays in vitro and estrogen/androgen (E/T) induced rat BPH model in vivo. NAF and the two enantiomers showed similar blocking activity on α 1 receptor. S -NAF exhibited more α 1D/1A adrenoceptor subtype selectivity than R -NAF and the racemate. The selectivity ratios pA 2 ( α 1D )/pA 2 ( α 1B ) and pA 2 ( α 1A )/pA 2 ( α 1B ) were 40.7- and 16.2-fold, respectively. NAF and its enantiomers effectively prevented the development of rat prostatic hyperplasia via suppressing the increase of the prostatic wet weight, visually. The quantitative analysis of the relative acinus volume, relative stroma volume, relative epithelial volume, epithelial height and expression of proliferating cell nuclear antigen (PCNA) and α -smooth muscle actin ( α -SMA) were carried out. S -NAF showed an advantage on the effect of inhibiting prostate wet weight and stroma volume over R -NAF and racemate NAF ( P R -NAF and S -NAF not only relax prostate muscle but also inhibit the prostate growth, thus relieve BPH.