Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon.

Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon were investigated. TM-906 in the concentrations of 10(-6) g/ml and 10(-5) g/ml increased the tone without affecting the amplitude of the spontaneous contraction in the preparations with low tone, whereas it decreased the tone and the amplitude of the spontaneous contraction in the preparations with high tone. At the higher concentration (10(-4) g/ml). TM-906 decreased the tone and finally abolished the spontaneous contraction in any preparation. The increase in tone induced by TM-906 was prevented by diltiazem and exposure to Ca++-free solution, but not by tetrodotoxin, atropine, phentolamine or propranolol, and depended on the extracellular concentration of CaCl2. On the other hand, the decrease in tone and amplitude of the spontaneous contraction produced by TM-906 were not prevented by tetrodotoxin, phentolamine or propranolol. TM-906 further increased the tone increased by 10 mM KCl, while it decreased the tone increased by 30 mM KCl. From results described above, it is suggested that TM-906 possesses both a relaxing effect and an excitatory effect which seem to be due to its direct action on the smooth muscle.