Review: The Role of MOP and DOP Receptors in Treatment of Diarrheapredominant Irritable Bowel Syndrome

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a frequent functional disorder of the gastrointestinal (GI) tract affecting nearly one fifth of the worldwide population. IBS-D is associated with numerous symptoms including diarrhea, bloating, abdominal pain and discomfort, which significantly reduce patients’ quality of life. Due to a complex and unclear pathogenesis, effective therapy against IBS-D has not been developed yet. Nowadays, treatment is focused on non-pharmacological (e.g. changes in diet and life style) and pharmacological (e.g. loperamide, ramosetron, rifaximin) approaches. The endogenous opioid system is responsible for the maintenance of homeostasis in the GI tract. Activation of the intestinal opioid receptors (ORs), in particular μ (MOP) and δ (DOP) results in reduction of epithelial secretion and increase of water/electrolyte absorption; moreover, opioids are strong analgesic agents. Thus, ligands of ORs are a promising target in IBS-D treatment. In this review, we discuss the role of ORs in the pathogenesis of IBS-D and the use of “classical” and novel, such as P-317, eluxadoline and biphalin MOP and DOP receptor ligands in preclinical and clinical trials.