Effects of 4-Ethylamino-2-butynyl(2-cyclohexyl-2-phenyl)glycolate Hydrochloride, a Metabolite of Oxybutynin, on Bladder Specimens and Rhythmic Bladder Contraction in Rats in Comparison With Oxybutynin

Oxybutynin has been used for neurogenic bladder disorders and is known to have anti-cholinergic and antispasmodic properties. However, the anti-cholinergic and antispasmodic properties of 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl)glycolate hydrochloride (N-desethyloxybutynin: DEOB), a metabolite of oxybutynin, have not been clarified. Therefore, in the present study, we studied these properties by using rat urinary bladder specimens in comparison with oxybutynin. Moreover, the effect of DEOB on rhythmic urinary bladder contraction was also evaluated using anesthetized rats. DEOB and oxybutynin concentration-dependently inhibited the carbachol-induced contraction, the pA2 values being 7.19 and 7.11, respectively. DEOB and oxybutynin also concentration-dependently inhibited the 100 mM KCl-induced contraction, the ED50 values being 12.1 and 10.4 μM, respectively. Intravenously administered DEOB and oxybutynin dose-dependently (0.03 – 0.3 mg/kg) inhibited the amplitude of the rhythmic bladder contraction to similar degrees, but had no affect on the frequency. From the above results, it was determined that DEOB has anti-cholinergic and antispasmodic properties and that these activities were almost equal to those of oxybutynin. Therefore, DEOB may play an important role during oxybutynin therapy for neurogenic bladder disorder.