Effect of NS-21, an Anticholinergic Drug with Calcium Antagonistic Activity, on Lower Urinary Tract Function in a Rat Model of Urinary Frequency

• Published in: International journal of urology 1997-07, Vol.4 (4), p.401-406
• Main Authors: Sasaki, Yasuo, Hamada, Kozo, Yamazaki, Chiemi, Seto, Toshie, Kimura, Yutaka, Ukai, Yojiro, Yoshikuni, Yoshiaki, Kimura, Kiyoshi
• Format: Article
• Language: English
• Subjects: Animals; Atropine - pharmacology; Benzilates - pharmacology; bladder capacity; Calcium Channel Blockers - pharmacology; Denervation; Disease Models, Animal; Flavoxate - pharmacology; hypogastric nerve transection; Hypogastric Plexus - surgery; Male; Mandelic Acids - pharmacology; NS-21; Parasympatholytics - pharmacology; Phenylacetates - pharmacology; rat; Rats; Rats, Sprague-Dawley; Urinary Bladder - chemistry; Urinary Bladder - drug effects; Urinary Incontinence - drug therapy
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1111/j.1442-2042.1997.tb00215.x

Background: NS‐21 is under development for the treatment of urinary frequency and urinary incontinence. The purpose of this study was to investigate the effects of NS‐21 and its active metabolite, RCC‐36, on lower urinary tract function in an experimental rat model of urinary frequency. Methods: Cystometrograms were recorded in anesthetized rats with bilaterally transected hypogastric nerves. All drugs were administered intraduodenally. Results: In sham‐operated rats, NS‐21 (≥ 50mg/kg) significantly increased the bladder capacity without significantly decreasing micturition pressure, while RCC‐36 (100mg/kg) significantly increased bladder capacity, and at a dose of a 30mg/kg, also caused a decrease in micturition pressure. This increase in bladder capacity appeared at lower doses of both NS‐21 and RCC‐36 in the hypogastric nerve‐transected rats. Propiverine (100mg/kg) increased bladder capacity and at a 30mg/kg, decreased micturition pressure in both sham‐operated and nerve‐transected rats. Oxybutynin (100mg/kg) and atropine (30mg/kg) decreased the micturition pressure in both sham‐operated and nerve‐transected rats without increasing the bladder capacity, while a similar anticholinergic calcium antagonist, terodiline (100mg/kg) had no effect on bladder capacity in either sham‐operated or nerve‐transected rats. Flavoxate (500mg/kg) significantly increased bladder capacity without significantly decreasing micturition pressure in both sham‐operated and nerve‐transected rats, while 50mg/kg of verapamil significantly increased bladder capacity without significantly decreasing the micturition pressure in nerve‐transected rats. Conclusions: NS‐21 and RCC‐36 increased bladder capacity at lower doses in hypogastric nerve‐transected rats than in sham‐operated rats. Furthermore, NS‐21 increased the bladder capacity without suppressing micturition pressure, suggesting that NS‐21 may be a more effective therapeutic drug than propiverine, oxybutynin or flavoxate for the treatment of urinary frequency and urinary incontinence.