Effects of trimebutine maleate (TM-906) on electrical and mechanical activities of smooth muscles of the guinea-pig stomach.
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 X 10(-5) M) depolarized the membrane of smooth muscles in the antrum to about 10 mV. From the current-voltage relationship and changes in membrane potentials in various [K]0, 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 first 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.
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D014287:Trimebutine / Q000494:pharmacology*
D001565:Benzoates; D011343:Procaine; D011189:Potassium Chloride; D014287:Trimebutine