Effects of Trimebutine Maleate (TM-906) on Electrical and Mechanical Activities of Smooth Muscles of the Guinea-Pig Stomach

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Abstract
The effects of trimebutine maleate (TM-906) on electrical and mechanical activities of smooth muscles of the guinea-pig stomach were investigated using a microelectrode and isometric tension recording methods. TM-906 (2 .times. 10-5 M) depolarized the membrane of smooth muscles in the antrum to .apprx. 10 mV. From the current-voltage relationship and changes in membrane potentials in various [K]o, the TM-906-induced depolarization is considered to be mainly due to a decrease in the K-conductance. TM-906 increased the amplitude of the 1st spike potential and regularized the rhythm of slow waves. These excitatory effects are presumably due to the K-channel-blocking action during the repolarizing phase of the spikes and to the depolarization. TM-906 reduced the amplitudes of mechanical activities and slow waves. These inhibitory effects are presumably due to the inhibition of Ca-release from storage sites and to the block of Ca-influx. The biphasic effects are possibly due to the local anesthetic properties. TM-906 modified neither the membrane potential nor the membrane conductance of circular muscles in the fundus. This may mean that the circular muscles in the fundus lack the K-channel sensitive to TM-906.