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[Effect of oxybutynin hydrochloride on isolated smooth muscles (ileum, urinary bladder and urethra)]
Abstract:
Effects of oxybutynin hydrochloride on isolated smooth muscle were investigated in preparations of isolated rabbit bladder body, bladder base, collum vesicae and urethra. ACh produced a marked contraction of the preparation from the bladder body and produced no response in the collum vesicae and the urethra; however, NE caused a marked contraction of the preparations from the collum vesicae and the urethra and relaxation in the bladder body. Oxybutynin and papaverine hardly had any effect on these preparations. Effects of oxybutynin on the contractile response of the isolated ileum or urinary bladder of rabbit, guinea pig and rat in comparison with atropine, papaverine, flavoxate and other drugs were investigated. The responsibility of these preparations to ACh were approximately 100 times higher in the ileum than in the urinary bladder. Oxybutynin showed a competitive inhibition to contractile response induced by ACh in the ileum and urinary bladder, whose potency was about 1/7-1/10 that of atropine. In the ileum of rats which were treated with oxybutynin orally at a dose of 1, 10 or 100 mg/kg for 60 days, the response to ACh in the preparations of the animals treated by 100 mg/kg were decreased, but the anticholinergic action in the groups treated with oxybutynin were not significantly different compared with the nontreated or saline treated group. On the other hand, oxybutynin showed a non-competitive inhibition to contractile response induced by Ba2+, Ca2+ and histamine in the guinea pig ileum and Ba2+, high-K+, Ca2+ and ATP in the rabbit urinary bladder. These potencies of oxybutynin were equal or slightly stronger than that of papaverine or flavoxate. However, oxybutynin had no effect on the contraction induced by NE in the rabbit urethra. The above results suggest that oxybutynin has atropine-like anticholinergic action and direct muscle relaxant action evidenced by non-competitive inhibition to contractile response induced by several agonists.