Genomic Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053, Japan.
J Pharmacol Sci. 2011;116(1):47-53. doi: 10.1254/jphs.11012fp. Epub 2011 Apr 27.
Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloon gastric distension to enable abdominal muscle contractions and characterized the visceromotor response (VMR) to such distension in conscious rats. We also investigated the effects of mosapride on gastric distension-induced VMR in the same model. Mosapride (3-10 mg/kg, p.o.) dose-dependently inhibited gastric distension-induced VMR in rats. However, itopride even at 100 mg/kg failed to inhibit gastric distension-induced VMR in rats. Additionally, a major metabolite M1 of mosapride, which possesses 5-HT(3)-receptor antagonistic activity, inhibited gastric distension-induced VMR. The inhibitory effect of mosapride on gastric distension-induced visceral pain was partially, but significantly inhibited by SB-207266, a selective 5-HT(4)-receptor antagonist. This study shows that mosapride inhibits gastric distension-induced VMR in conscious rats. The inhibitory effect of mosapride is mediated via activation of 5-HT(4) receptors and blockage of 5-HT(3) receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.
枸橼酸莫沙必利（mosapride）是一种具有 5-HT（4）受体激动活性的促动力药物，已知可增强胃排空并缓解功能性消化不良（FD）患者的症状。由于痛觉过敏和胃排空延迟在 FD 的发病机制中起重要作用，我们在这项研究中使用气囊胃扩张来使腹部肌肉收缩，并在清醒大鼠中描述了这种扩张的内脏运动反应（VMR）。我们还研究了 mosapride 对同一模型中胃扩张诱导的 VMR 的影响。Mosapride（3-10mg/kg，po）剂量依赖性地抑制大鼠胃扩张诱导的 VMR。然而，即使给予 100mg/kg 的伊托必利，也不能抑制大鼠胃扩张诱导的 VMR。此外，mosapride 的主要代谢物 M1 具有 5-HT（3）受体拮抗活性，可抑制胃扩张诱导的 VMR。Mosapride 对胃扩张诱导的内脏痛的抑制作用部分但显著被 5-HT（4）受体选择性拮抗剂 SB-207266 抑制。这项研究表明，mosapride 抑制清醒大鼠胃扩张诱导的 VMR。Mosapride 的抑制作用是通过激活 5-HT（4）受体和由 mosapride 代谢物阻断 5-HT（3）受体介导的。这一发现表明，mosapride 通过增加疼痛阈值可能有助于缓解 FD 相关的胃肠道症状。
