INHIBITION OF PROSTAGLANDIN-INDUCED INTESTINAL SECRETION BY IGMESINE IN HEALTHY-VOLUNTEERS

Background & Aims: Igmesine, a sigma ligand, has been shown to inhibit intestinal secretion and diarrhea in animal models. The purpose of th is study was to measure the inhibitory effect of igmesine on basal and prostaglandin E-2 (PGE(2))-induced jejunal secretion in normal volunt eers. Methods: Jejunal absorption of water and electrolytes was measur ed with a three-lumen open-segment perfusion method in 16 volunteers. A double-blind crossover study was performed involving intraluminal in fusion of PGE(2) after oral administration of placebo or igmesine at h ive doses. Results: PGE(2) induced net secretion of water and electrol ytes (P < 0.01 vs. basal conditions). The effect of PGE(2) on water an d 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 si ngle oral dose. Igmesine at a dose of 200 mg also produced a significa nt decrease in basal rates of water and electrolyte absorption. Conclu sions: Igmesine, a a ligand, inhibits PGE(2)-induced intestinal secret ion in normal humans. Evaluating the drug in chronic diarrheas may be of interest.