Takenaga H, Magaribuchi T, Tamaki H
Jpn J Pharmacol. 1984 Aug;35(4):439-43. doi: 10.1254/jjp.35.439.
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.
研究了马来酸曲美布汀（TM - 906）对豚鼠离体胆囊平滑肌的作用。TM - 906对胆碱能神经刺激（5赫兹）和乙酰胆碱（3×10⁻⁸克/毫升）引起的收缩反应具有同等程度的抑制作用，二者产生的收缩幅度大致相同。TM - 906对乙酰甲胆碱的收缩反应具有非竞争性拮抗作用，并且它使氯化钙收缩反应的剂量 - 反应曲线平行右移至更高浓度。此外，TM - 906以剂量依赖性方式抑制对50毫摩尔氯化钾的收缩反应。另一方面，TM - 906自身以剂量依赖性方式引起轻微的收缩反应。暴露于无钙溶液可阻止TM - 906诱导的收缩反应，但河豚毒素或阿托品则不能。从这些结果推测，TM - 906通过减少钙离子跨细胞膜内流来抑制对胆碱能神经刺激、乙酰胆碱、乙酰甲胆碱和50毫摩尔氯化钾的收缩反应，而推测TM - 906自身通过以某种方式增加可用于收缩系统的细胞内游离钙离子浓度来引起轻微的收缩反应。
