T1381 Inhibition of Colonic Motility and Defecation By RS-127445 Suggests Involvement of the 5-HT2b Receptor in Large Bowel Physiology

ileus model.Charcoal was administered through orogastric tubes.The distance of charcoal migration from pylorus to the distal intestine was measured at 3 hours after administration of itopride 1, 3, 10, and 30 mg/kg, consecutively.Additional experiments with infusion of dopamine and atropine was carried out to investigate its mechanism.Results : The gastrointestinal transit assessed by migration distance was significantly decreased in postoperative ileus group compared with sham operation group(121.7±22.5cmvs 13.3±23.0cm,p<0.05).Itopride showed significant increase in the charcoal movement through the intestine.compared with vehicle group.A combination of dopamine or atropine with itopride displayed considerable decrease in the migration distance compared with that of itopride alone.Conclusions : Postoperative ileus model exhibited decrease in gastrointestinal motiliy, and conversely, infusion of itopride promoted it through antidopaminergic and cholinergic mechanism.These results lay experimental backgrounds for using itopride for treatment of postoperative ileus.