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.

Abstract

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.

• Authors: Y Kimura, H Fukui, K Hamada, T Ogasawara, C Yamazaki, Y Ukai, Y Yoshikuni, K Kimura
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 47 Issue 2 Pg. 182-9 (Feb 1997) ISSN: 0004-4172 [Print] Germany
• PMID: 9079238 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Cholinergic Antagonists
• Phenylacetates
• RCC 36
• temiverine

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Cholinergic Antagonists (pharmacology)
• Decerebrate State (physiopathology)
• Dogs
• Electromyography (drug effects)
• Phenylacetates (pharmacology)
• Urinary Bladder (drug effects)
• Urinary Tract (drug effects)
• Urination (drug effects)
• Urodynamics (drug effects)