An overview of 5-HT3 receptor antagonists as a treatment option for irritable bowel syndrome with diarrhea

Abstract

Introduction: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, discomfort, and altered bowel habits, which affects the quality of life of approximately 10% of the worldwide population. IBS is classified into three types: IBS-D (diarrhea-predominant), IBS-C (constipation-predominant), and mixed or alternating IBS (IBS-M). Among the potential interventions for IBS-D, the antagonism of the serotonin 5-HT₃ receptor has recently emerged as an effective treatment option. Serotonin (5-HT) is a neurotransmitter and an immunoregulatory factor, which plays a key role in physiological and pathological processes of the human body, having an impact on intestinal motility and gland secretion, which assist in maintaining intestinal homeostasis.

Areas covered: In this paper, the concept of 5-HT₃ antagonists in the treatment of individuals with IBS-D is discussed, with particular focus on mechanism of action and pre-clinical and clinical data. This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases.

Expert opinion: Recent clinical trial data have confirmed beyond doubt the value of 5-HT₃ antagonists. As for future directions, weak partial 5-HT₃ receptor agonism appears to be an appealing alternative to a silent antagonist for the treatment of IBS-D.

Keywords: 5-HT3; clinical studies; colitis; diarrhea; intestinal motility; irritable bowel syndrome; treatment.