Effect of NS-21, an anticholinergic drug with calcium antagonistic activity, on lower urinary tract function in a rat model of urinary frequency.
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 (> or = 50 mg/kg) significantly increased the bladder capacity without significantly decreasing micturition pressure, while RCC-36 (100 mg/kg) significantly increased bladder capacity, and at a dose of > or = 30 mg/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 (100 mg/kg) increased bladder capacity and at > or = 30 mg/kg, decreased micturition pressure in both sham-operated and nerve-transected rats. Oxybutynin (100 mg/kg) and atropine (30 mg/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 (100 mg/kg) had no effect on bladder capacity in either sham-operated or nerve-transected rats. Flavoxate (500 mg/kg) significantly increased bladder capacity without significantly decreasing micturition pressure in both sham-operated and nerve-transected rats, while 50 mg/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.
Sasaki
Y
Y
Research Laboratories, Nippon Shinyaku Co. Ltd., Minami-ku, Kyoto, Japan.
Hamada
K
K
Yamazaki
C
C
Seto
T
T
Kimura
Y
Y
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003714:Denervation; D004195:Disease Models, Animal; D005422:Flavoxate / Q000494:pharmacology; D007001:Hypogastric Plexus / Q000601:surgery; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000737:chemistry / Q000187:drug effects; D014549:Urinary Incontinence / Q000188:drug therapy*
D001561:Benzilates; D002121:Calcium Channel Blockers; D008333:Mandelic Acids; D010276:Parasympatholytics; D010648:Phenylacetates; C107100:RCC 36; D005422:Flavoxate; C015586:propiverine; D001285:Atropine; C105354:temiverine; C005419:oxybutynin