Dexloxiglumide for the treatment of constipation predominant irritable bowel syndrome

Irritable bowel syndrome (IBS) is a multifactorial functional gut disorder, where sensory/motor disturbances seem to play a major role, with no satisfactory treatment for a majority of patients. Cholecystokinin (CCK) is a hormone with several effects on gastrointestinal function, and IBS patients have been shown to produce altered sensory/motor responses to CCK.

Dexloxiglumide is a selective antagonist of the type 1 receptor of CCK, which has demonstrated to revert the CCK mediated effects on gastrointestinal motility and sensitivity. In humans, Dexloxiglumide has been shown to accelerate gastric emptying, slow down transit in the proximal colon, and increase the tolerance to intestinal gas. In phase 2 clinical trials Dexloxiglumide 200 mg tid has demonstrated to be superior to placebo in symptom relief in constipation predominant IBS (IBS-C). In a phase 3 withdrawal study Dexloxiglumide obtained a more sustained effect than placebo. However, these promising effects in IBS-C have not been confirmed in large phase 3 studies so far.

Dexloxiglumide has demonstrated positive effects on important aspects of gastrointestinal function, like gastric emptying and gas tolerance, that deserves consideration in future studies. However, the available data is insufficient to recommend dexloxiglumide for treatment of IBS-C today.