Inhibition of prostaglandin-induced intestinal secretion by igmesine in healthy volunteers

Abstract

Background & Aims: Igmesine, a σ ligand, has been shown to inhibit intestinal secretion and diarrhea in animal models. The purpose of this study was to measure the inhibitory effect of igmesine on basal and prostaglandin E 2 (PGE 2)-induced jejunal secretion in normal volunteers. Methods: Jejunal absorption of water and electrolytes was measured with a three-lumen open-segment perfusion method in 16 volunteers. A double-blind crossover study was performed involving intraluminal infusion of PGE 2 after oral administration of placebo or igmesine at two doses. Results: PGE 2 induced net secretion of water and electrolytes ( P < 0.01 vs. basal conditions). The effect of PGE 2 on water and electrolytes was not changed by 25 mg of igmesine but was suppressed by 200 mg of igmesine. This effect lasted at least 3 hours after a single oral dose. Igmesine at a dose of 200 mg also produced a significant decrease in basal rates of water and electrolyte absorption. Conclusions: Igmesine, a σ ligand, inhibits PGE 2-induced intestinal secretion in normal humans. Evaluating the drug in chronic diarrheas may be of interest. GASTROENTEROLOGY 1998;115:591-596