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Trimebutine maleate effect on sensory thresholds

Time:2015/9/16 2:14:45

Enhancement of visceral perception has been demonstrated in patients with functional bowel disorders, and particularly in patients with IBS. The colonic thresholds of pain perception are lowered in these patients compared with controls." Pharmacological manipulation of these visceral perception thresholds is an interesting target for new drugs in the field ofIBS. 9 1 Results from a recent study in animals showed that Trimebutine maleate may influence the activity of visceral afferents." In conscious rats, and in humans, rectal distension induces a rectocolonic reflex characterized by inhibition of colonic motility. In this model, Trimebutine maleate significantly decreased the intensity of this inhibitory reflex at a dose of 5 mg/kg (intraperitoneally). Further, the abdominal contractions induced by rectal distension were reduced by Trimebutine maleate at the intraperitoneal dose of 10 mg/kg." In another model, hypersensitivity to rectal distension was induced in rats by rectal inflammation with trinitrobenzenesulphonic acid (L Bueno, Personal Communication)." In inflamed animals, the threshold volume of rectal distension producing abdominal cramps was lowered to 0.4 ml compared with 0.8 ml in non-inflamed rats. After treatment of the animals with Trimebutine maleate (10 and 20mg/kg, intraperitoneally), a normal threshold for abdominal cramps, i.e. 0.8 ml, was restored. These results demonstrate that Trimebutine maleate is able to modify visceral sensitivity by reducing the visceral pain produced by colorectal distension. This action of Trimebutine maleate on visceral sensory afferents may explain partly its beneficial effect in the treatment ofIBS (see below).