Premium
Uroselectivity in male dogs of silodosin (KMD‐3213), a novel drug for the obstructive component of benign prostatic hyperplasia
Author(s) -
Tatemichi Satoshi,
Tomiyama Yoshitaka,
Maruyama Itaru,
Kobayashi Shinya,
Kobayashi Kumi,
Maezawa Ayaka,
Kobayashi Mamoru,
Yamazaki Yoshinobu,
Shibata Nobuo
Publication year - 2006
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20312
Subject(s) - silodosin , tamsulosin , medicine , urology , hyperplasia , international prostate symptom score , in vivo , antagonist , benign prostatic hyperplasia (bph) , prostate , lower urinary tract symptoms , receptor , cancer , microbiology and biotechnology , biology
Aims Our main aim was to compare the prostatic selectivity of silodosin with that of other α 1 ‐adrenoceptor (AR) antagonists. Methods We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)‐induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)‐induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. Results In vitro, all drugs antagonized NA‐induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose‐dependently inhibited the HNS‐induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED 15 /ID 50 ) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). Conclusions Our results clearly demonstrate that silodosin is a potent and highly selective α 1A ‐AR antagonist. A selective α 1A ‐AR antagonist such as silodosin may have good potential as a less‐hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients. Neurourol. Urodynam. 25:792–799, 2006. © 2006 Wiley‐Liss, Inc.