Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus.

Preclinical animal study investigating the effects of ipamorelin on gastric emptying and smooth muscle contractility in a rodent model of postoperative ileus.

“The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation.”

Adult male Sprague-Dawley rats subjected to laparotomy and intestinal manipulation to induce postoperative ileus.

“Experiments were performed using adult male Sprague-Dawley rats (225–275 g) obtained from Charles River (Wilmington, MA).”

Groups consisted of 5 to 10 rats for in vivo studies and 10 to 11 experiments for in vitro studies.

“Data are mean ± SEM for 5–10 rats in each group.”

Gastric emptying was measured 15 minutes after intragastric gavage; the surgical procedure lasted 25–30 minutes.

“Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of 99mTc (technicium-99m) sulfur colloid in 0.5% methylcellulose.”

Ipamorelin administration significantly accelerated gastric emptying in rats with postoperative ileus, reducing the amount of meal remaining in the stomach compared to vehicle controls.

“Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%.”

Ipamorelin normalized the inhibited contractile responses of gastric smooth muscle to acetylcholine and electrical field stimulation in isolated preparations from rats with postoperative ileus.

“Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin.”

The prokinetic effects of ipamorelin on gastric emptying and intestinal transit were associated with the activation of ghrelin receptor-mediated mechanisms involving cholinergic excitatory neurons.

“These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.”

The study was conducted in a rodent model of postoperative ileus, and potential anti-inflammatory effects of ipamorelin were not investigated in this specific study.

“Although not investigated in the current study, the possibility exists that ipamorelin, in addition to acting as a gastroproketic, may also possess anti-inflammatory effects.”