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Oxybutynin has been used for neurogenic bladder disorders in clinic and known to have anti-cholinergic and spasmolytic properties. Metabolite of oxybutynin, 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl) glycolate (N-desethyloxybutynin: DEOB) has been known to have similar anti-cholinergic and spasmolytic properties. However, the effect of DEOB on the urinary bladder has not been clarified in situ. Therefore, in the present study, we studied the effect of DEOB on acetylcholine-induced urinary bladder contraction in comparison with oxybutynin in anesthetized dogs. Intravenously administered DEOB dose-dependently inhibited acetylcholine-induced contractions. Oxybutynin also showed similar efficacy. From the Schild plot, it was found that the slope of DEOB and oxybutynin were 0.78 (95% confidence limit: 0.45-1.11) and 1.49 (95% confidence limit: 0.91-2.08), respectively. The dose of DEOB or oxybutynin needed to shift the concentration-dependent curve of acetylcholine rightward to a two times higher dose was calculated. The doses of DEOB and oxybutynin were 6.4 micro g/kg (95% confidence limit: 1.7-12.8 micro g/kg) and 13.9 micro g/kg (95% confidence limit: 6.3-24.5 micro g/kg), respectively. From the above results, it was found that DEOB has the same anti-cholinergic property as oxybutynin and that its activity was almost equipotent to that of oxybutynin. Therefore, DEOB was suggested to play an important role during oxybutynin therapy for neurogenic bladder disorder.

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Effect of 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl) glycolate, metabolite of oxybutynin, on intra-artery administered acetylcholine-induced urinary bladder contraction in anesthetized dogs