Effects of Mosapride citrate (cas 112885-42-4), a 5-HT4–Receptor Agonist, on Gastric Distension–Induced Visceromotor Response in Conscious Rats

Add time:08/02/2019    Source:sciencedirect.com

.Mosapride citrate (mosapride), a prokinetic agent with 5-HT4–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-HT3–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-HT4–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-HT4 receptors and blockage of 5-HT3 receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.

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