Comparison of pinaverium bromide, manganese chloride and D600 effects on electrical and mechanical activities in rat uterine smooth muscle

The effects of pinaverium bromide, were compared with those of D600 and manganese chloride (Mn), on membrane potentials, ionic currents and isometric contractions in uterine smooth muscle strips from pregnant rats. Pinaverium bromide (10(-7) - 10(-6) M) depressed twitch contractions and K-contractures within 15-20 min while D600 (2 X 10(-6) M) and Mn (10(-3) M) abolished both contractions. D600 and pinaverium bromide were more potent inhibitors in K-depolarized preparations than in polarized tissues. At a supramaximal dose (10(-5) M), pinaverium bromide decreased the rate of rise, amplitude, and rate of repolarization of the action potential, and prolonged the potential duration. The inward Ca current was depressed and the reduction in Cai was responsible for the decrease in K current. Pinaverium bromide (10(-5) M) depressed the myometrial contractions induced in Ca-free solution by acetylcholine (10(-4) M) and by prolonged membrane depolarizations. Mn (2.5 X 10(-3) M) only reduced the Ach-induced contraction and D600 (10(-5) M) had no effect on intracellular Ca stores. The results indicate that pinaverium bromide has Ca channel blocking properties similar to those of currently used Ca antagonists; it may also exert an effect to depress contractions supported by intracellular Ca release.