Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats.
OBJECTIVE
The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT(3)) receptor antagonist, and a novel enterokinetic agent, prucalopride, a 5-HT(4) receptor agonist.


METHODS
Different degrees of inhibition of gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy, or laparotomy plus mechanical stimulation of the gut.


RESULTS
Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations. Granisetron had no effect on the transit after the three operations when given alone. Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone. However, statistical significance was only reached when prucalopride was combined with granisetron. Erythromycin, a motilin receptor agonist, did not improve postoperative ileus in the rat.


CONCLUSIONS
Cisapride, but not metoclopramide or erythromycin, is able to improve postoperative ileus in the rat. The results suggest that a combination of 5-HT(3) receptor antagonist and 5-HT(4) receptor agonist properties may be required to obtain a beneficial effect on surgery induced ileus in the rat. 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.
De Winter
B Y
BY
Division of Gastroenterology and Pharmacology, Faculty of Medical and Pharmaceutical Sciences, University of Antwerp, Wilrijk, Belgium.
Boeckxstaens
G E
GE
De Man
J G
JG
Moreels
T G
TG
Schuurkes
J A
JA
Peeters
T L
TL
Herman
A G
AG
Pelckmans
P A
PA
D000818:Animals; D020117:Cisapride / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000627:therapeutic use; D004917:Erythromycin / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D017829:Granisetron / Q000627:therapeutic use; D007415:Intestinal Obstruction / Q000517:prevention & control*; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000627:therapeutic use
D020117:Cisapride; D018492:Dopamine Antagonists; D004917:Erythromycin; D005765:Gastrointestinal Agents; D017829:Granisetron; D008787:Metoclopramide; D012702:Serotonin Antagonists