Effects of propiverine hydrochloride (P-4) and its metabolites on urinary bladder function in anesthetized rats

The effects of P-4 and its active metabolites, 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide[P-4(N----O)], 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4 (N----O)] and 1-methyl-4-piperidyl benzilate hydrochloride (DPr-P-4), on urinary bladder function were investigated in urethane anesthetized rats. By cystometrography, P-4 (2, 4 mg/kg, i.v.) and P-4 (N----O) (4 mg/kg, i.v.), which have direct action on smooth muscles, significantly increased the maximum vesical volume. As for rhythmic bladder contractions, P-4 (1,2,4 mg/kg, i.v.) and P-4 (N----O) (2, 4 mg/kg, i.v.) significantly decreased the frequency with a slight decrease in the amplitude. On the other hand, DPr-P-4 (N----O) (0.1, 0.5 mg/kg, i.v.) and DPr-P-4 (0.01, 0.05 mg/kg, i.v.), which have anticholinergic effects, significantly inhibited the maximum vesical pressure on the cystometrograms, and DPr-P-4 (N----O) (0.1, 0.5 mg/kg, i.v.) and DPr-P-4 (0.005, 0.05 mg/kg, i.v.) significantly inhibited the amplitude of the rhythmic bladder contractions. The effects of flavoxate and papaverine were similar to those of P-4 and P-4 (N----O), but the effects of propantheline and atropine were similar to those of DPr-P-4 (N----O) and DPr-P-4 in these two experimental methods. These results suggest that the clinical effects of P-4 are based not only on the actions of P-4 itself but also on those of its active metabolites.