https://orcid.org/0000-0002-5306-3158
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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.
Article highlights
Although the precise pathophysiology of IBS is unknown, its complex character is obvious, with environmental and host variables playing a role. The treatment of IBS patients is difficult, and a tailored strategy is required. A solid, reassuring physician-patient connection is essential, followed by patient education, dietary recommendations, and stress reduction.
Serotonin receptor 5-HT3 antagonists, such as alosetron, cilansetron, and ramosetron, have been shown in numerous large clinical trials to be among the most effective treatment options to date for both male and female IBS-D patients. Granisetron and ondansetron are two more medications that are prescribed to alleviate nausea and vomiting, although they are not as effective as alosetron in the lower gastrointestinal tract.
Through central and peripheral mechanisms, the 5-HT3 antagonists reduce certain IBS symptoms like frequent bowel movements, a sense of urgency, and chronic abdominal pain and discomfort.
It has been demonstrated that the new 5-HT3 antagonists reduce the frequency, urgency, and pain of stools as well as other symptoms associated with IBS-D.
Due to the possibility of ischemic colitis and constipation-related problems, 5-HT3 antagonist-based therapies necessitate the establishment of a risk management strategy and hence weak partial 5-HT3 receptor agonism should be considered.
Abbreviations
| 5–HT | = | 5-hydroxytryptamine |
| CAT | = | catalase |
| CNS | = | central nervous system |
| COX-2 | = | cyclooxygenase-2 |
| CRP | = | C-reactive protein |
| EC | = | enterochromaffin cells |
| eNOS | = | endothelial nitric oxide synthase |
| FDA | = | Food and Drug Administration |
| FGIDs | = | functional gastrointestinal disorders |
| GI | = | gastrointestinal |
| GSK3b | = | glycogen synthase kinase 3 |
| HO-1 | = | heme oxygenase-1 |
| IBS | = | irritable bowel syndrome |
| IBS-C | = | irritable bowel syndrome with constipation |
| IBS-D | = | irritable bowel syndrome with diarrhea |
| IBS-M | = | irritable bowel syndrome with mixed bowel habits |
| IBS-U | = | irritable bowel syndrome |
| iNOS | = | inducible nitric oxide synthase |
| JAK | = | Janus kinase |
| NFAT | = | nuclear factor of activated T cells |
| NFκB | = | nuclear factor κB |
| Nrf2 | = | nuclear factor erythroid 2–related factor 2 |
| NTS | = | nucleus tractus solitarii |
| PI3K | = | phosphoinositide 3-kinase |
| ROS | = | reactive oxygen species |
| STAT | = | signal transducer and activator of transcription |
| TNF-α | = | tumor necrosis factor α |
| RCT | = | randomized clinical trial |
| QT | = | electrocardiographic recording from the beginning of the Q-wave to the end of the T-wave |
| P450 (CYP)1A2 | = | cytochrome P450 1A2 |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Authors contributions
A Tarasiuk and J Fichna provided the overall concept and framework of the review; K Merecz, M Hirsa, O Biniszewska and A Tarasiuk researched and identified appropriate articles, and wrote the manuscript; K Merecz, M Hirsa, O Biniszewska and A Tarasiuk revised the manuscript. All authors read and approved the final version of the manuscript.