Abstract
The effects of P-4 and its active metabolites in human blood and urine and the effects of 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide CP-4(N→O)), 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4(N→O)) and 1-methyl-4-piperidyl benzilate (DPr-P-4) on isolated guinea pig urinary bladder were investigated. At doses of 10-6 or 10-5 M, P-4 shifted the dose-response curve for acetylcholine (ACh) to the right, and at a dose of 10-5 M, it also inhibited the maximum response of ACh. At doses of 10-5 M or more, P-4(N→O) inhibited the maximum response of ACh. DPr-P-4(N→O) or DPr-P-4 shifted the dose-response curve for ACh to the right at doses of 10-6 ?? 10-4 M or at doses of 10-7 ?? 10-5 M. P-4 at doses of 10-6 M or more inhibited the KCl (100 mM)-induced contraction in a dose-dependent manner, and its potency was quite equal to that of terodiline. The inhibitory effect of P-4(N→O), DPr-P-4(N→O) and DPr-P-4 in the KCl (100 mM)-induced contraction were weaker than that of P-4. P-4 and P-4(N→O) had a dose-dependent inhibitory effect on K+-induced 45Ca influx in isolated guinea-pig urinary bladder. These results indicated that P-4 had mainly a direct action on the smooth muscle of isolated guinea pig urinary bladder, and P-4(N→O) had the same effect as those of P-4 and DPr-P-4(N→O) or DPr-P-4 had an anticholinergic effect.
