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 rhesus monkeys.

NS-21 ((+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) and its active metabolite, RCC-36 ((+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride), have both anticholinergic and calcium antagonistic activities. NS-21 is under development for the treatment of bladder dysfunction. This study was designed to compare the effects of NS-21 and RCC-36 on the bladder function of monkeys with the effects of various reference drugs. Male rhesus monkeys were anesthetized with a mixture of enflurane and nitrous oxide, a transurethral catheter was inserted into the urinary bladder from the external urethral orifice, and cystometrograms were recorded. Drugs were administered intravenously. NS-21 at doses of 0.3 and 1 mg/kg caused an increase in bladder capacity without affecting the micturition pressure. RCC-36 also caused an increase in bladder capacity, but it was accompanied by a significant decrease in micturition pressure. Oxybutynin, atropine and verapamil all caused decreases in micturition pressure at doses which caused an increase in bladder capacity. Of the drugs examined, only NS-21 caused an increase in the bladder capacity of rhesus monkeys without affecting the micturition pressure. This drug is therefore a promising candidate for the clinical treatment of pollakiuria and urinary incontinence.