title: 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.
abstract: 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.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Hamada
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: T
authors.initials: T
authors.lastname: Ogasawara
authors.forename: Y
authors.initials: Y
authors.lastname: Ukai
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikuni
authors.forename: K
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D003558:Cystoscopy; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects; D014551:Urinary Tract / Q000187:drug effects*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D010648:Phenylacetates; C107100:RCC 36; C105354:temiverine