Title:Review: The Role of MOP and DOP Receptors in Treatment of Diarrheapredominant Irritable Bowel Syndrome
VOLUME: 16 ISSUE: 18
Author(s):Agata Jarmuż, Marta Zielińska, Karolina Leń, Martyna Banaszek, Martin Storr and Jakub Fichna
Affiliation:Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Keywords:Diarrhea, irritable bowel syndrome, MOP/DOP receptor ligands, opioid receptors, opioids.
Abstract: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.