Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats

Background/Aim-The effects of different prokinetic agents, the motilide ery thromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were com pared with that of granisetron, a 5-hydroxytryptamine (5-HT3) receptor anta gonist, and a novel enterokinetic agent, prucalopride, a 5-HT4 receptor ago nist. Methods-Different degrees of inhibition of gastrointestinal transit, measur ed by the migration of Evans blue, were achieved by skin incision, laparoto my, or laparotomy plus mechanical stimulation of the gut. Results-Metoclopramide decreased the transit after laparotomy with or witho ut mechanical stimulation, whereas cisapride increased it after all three o perations. Granisetron had no effect on the transit after the three operati ons when given alone. Prucalopride tended to increase the transit after lap arotomy with or without mechanical stimulation when given alone. However, s tatistical significance was only reached when prucalopride was combined wit h granisetron. Erythromycin, a motilin receptor agonist, did not improve po stoperative ileus in the rat. Conclusions-Cisapride, but not metoclopramide or erythromycin, is able to i mprove postoperative ileus in the rat. The results suggest that a combinati on of 5-HT3 receptor antagonist and 5-HT4 receptor agonist properties may b e required to obtain a beneficial effect on surgery induced ileus in the ra t. Furthermore, they indirectly indicate that stimulation of the excitatory mechanisms is not able to overcome the inhibitory influence of the neural reflex pathways activated during abdominal surgery.