Effect of the anticholinergic drug with calcium antagonistic activity, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, on lower urinary tract function in decerebrated dogs.
NS-21 ((+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) is a novel compound designed for the treatment of bladder dysfunction. The effects of NS-21 and its active metabolite, RCC-36 ((+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride), on the urodynamics of decerebrated dogs are reported. Dogs were decerebrated at the precollicular-postmamillary level and the urodynamic effects of intravenously administered NS-21, RCC-36, and various reference drugs were compared by cystometry. NS-21 (0.3-1 mg/kg) and RCC-36 (0.1 mg/kg) caused an increase in bladder capacity without affecting the micturition pressure or residual volume, and thus caused a significant increase in functional bladder capacity. Oxybutynin caused a dose-dependent increase in bladder capacity at 0.1 mg/ kg and higher doses; however, the associated decrease in micturition pressure resulted in a significant increase in residual volume and a decrease in functional bladder capacity. These effects of oxybutynin were similar to those of atropine. Propiverine (0.1-10 mg/kg) and terodiline (0.1-10 mg/kg) caused no significant increase in bladder capacity. In conclusion, in decerebrated dogs, NS-21 and RCC-36 increased the bladder capacity without increasing the residual volume. NS-21 thus had more favorable therapeutic effects than any of the reference drugs tested and is therefore a promising candidate drug for the treatment of pollakiuria and urinary incontinence.
Kimura
Y
Y
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Fukui
H
H
Hamada
K
K
Ogasawara
T
T
Yamazaki
C
C
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003655:Decerebrate State / Q000503:physiopathology*; D004285:Dogs; D004576:Electromyography / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects; D014551:Urinary Tract / Q000187:drug effects*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects*
D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D010648:Phenylacetates; C107100:RCC 36; C105354:temiverine