ISSN:
1442-2042
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1442-2042.1997.tb00215.x
