Effects of Trimebutine Maleate (TM-906) on the Smooth Muscles of Isolated Guinea Pig Gallbladder

Effects of trimebutine maleate (TM-906) on the smooth muscles of isolated guinea pig gallbladder were investigated. TM-906 inhibited the contractile responses to cholinergic nerve stimulation (5 Hz) and to acetylcholine (3 X 10(-8) g/ml) to the same extent, both of which produced much the same amplitude of contraction. TM-906 noncompetitively antagonized the contractile response to methacholine, and it caused a parallel shift of dose-response curves for the contractile response to CaCl2 to higher concentrations. Moreover, TM-906 inhibited the contractile response to 50 mM KCl in a dose-dependent manner. On the other hand, TM-906 itself evoked a slight contractile response in a dose-dependent manner. The contractile response induced by TM-906 was prevented by exposure to Ca++-free solution, but not by tetrodotoxin or atropine. From these results, it was suggested that TM-906 inhibited the contractile responses to cholinergic nerve stimulation, acetylcholine, methacholine and 50 mM KCl by reducing the influx of calcium ion across the cell membrane, while it was assumed that TM-906 itself evoked a slight contractile response by increasing in some way the concentration of the intracellular free calcium ion available for the contractile systems.