Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder characterized by recurrent abdominal pain and prolonged GI transit. The pathogenesis of IBS-C has still not been established; therefore, drugs currently in use in IBS-C act mainly symptomatically, whereas novel pharmacological targets are urgently needed. Tenapanor is a potent inhibitor of Na(+)/H(+) exchanger 3 [NHE3], localized in the apical membrane of intestinal epithelial cells. NHE3 participates in the uptake of sodium ions and water from the intestinal lumen.
Areas covered: In this review, the authors discuss pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies. They also summarize clinical trials on tenapanor's safety and efficacy in view of its potential role in IBS-C therapy.
Expert opinion: Tenapanor possesses an excellent preclinical safety profile and, as of now, there are no serious concerns about its side effects. The non-systemic action of tenapanor constitutes a significant advantage, as it minimizes possible adverse effects or drug-drug interactions. However, Phase III clinical trials are still needed to confirm results obtained in earlier phases and optimize the dose-response for tenapanor, whereas limiting diarrhea, its major adverse effect.
Keywords: NHE3 inhibitor; abdominal pain; constipation; gastrointestinal motility; irritable bowel syndrome; tenapanor.