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

ABSTRACT

BACKGROUND & AIMS: Igmesine, a final sigma 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 E2 (PGE2)-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 PGE2 after oral administration of placebo or igmesine at two doses. RESULTS: PGE2 induced net secretion of water and electrolytes (P < 0.01 vs. basal conditions). The effect of PGE2 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 final sigma ligand, inhibits PGE2-induced intestinal secretion in normal humans. Evaluating the drug in chronic diarrheas may be of interest.