[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.
Nomura
N
N
Biological Research Laboratories, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Kaneko
S
S
Hamakawa
T
T
Nagai
M
M
Iriki
M
M
D000818:Animals; D001561:Benzilates / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D001561:Benzilates; D010276:Parasympatholytics; C015586:propiverine