Drug discovery approaches to irritable bowel syndrome

  title={Drug discovery approaches to irritable bowel syndrome},
  author={Pamela J Hornby},
  journal={Expert Opinion on Drug Discovery},
  pages={809 - 824}
  • P. Hornby
  • Published 21 July 2015
  • Medicine
  • Expert Opinion on Drug Discovery
Introduction: Irritable bowel syndrome (IBS) is defined by symptoms of abdominal pain and altered bowel habits without detectable organic disease. Antidepressants and serotonin receptor modulators are used to treat IBS, but rare serious adverse events highlight the safety hurdle. Newer drugs with secretory and motility effects via local gut mechanisms have been successfully approved for IBS, often by registering first in a related, non-IBS condition to optimize dosing, formulation and… 
How can we develop better antispasmodics for irritable bowel syndrome?
The complex nature of IBS means that future successful drug discovery will require a multi-disciplinary approach, and a deeper insight into the underlying mechanisms involved in IBS-induced dysmotility and to uncover GI-specific receptors that regulating motility is essential.
Irritable bowel syndrome in children: new in diagnostics and treatment
The modern scientific concept of the shaping of irritable bowel syndrome (IBS) in children is presented, and various groups of pharmacological agents used in the treatment of IBS, mechanisms of action of artispasmodic drugs of new generations, features of the use ofprebiotics and probiotics, as well as medications for psychosomatic correction are considered.
Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome
Crofelemer did not significantly improve abdominal pain over placebo by the primary endpoint, however, it did based on the FDA abdominal pain monthly responder endpoint, which suggests that croFelemer may have a role in the treatment of abdominal pain associated with IBS-D.
G protein‐coupled estrogen receptor and estrogen receptor ligands regulate colonic motility and visceral pain
  • M. Zielińska, J. Fichna, +4 authors M. Storr
  • Biology, Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2017
The aim of this study was to determine the role of activation of classical estrogen receptors (ER) and novel membrane receptor, G protein‐coupled estrogen receptor (GPER) in human and mouse tissue and to assess the possible cross talk between these receptors in the GI tract.
Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.
This chapter provides the most current knowledge of the critical autocrine and paracrine roles of 5-HT in intestinal motility and inflammation as well as its function as a hormone in osteocyte homeostasis.
Enteric Neuronal Regulation of Intestinal Inflammation
Important concepts in the phylogeny of neuroimmunity, enteric neuronal and glial regulation of immunity, changes that occur in the enteric nervous system during inflammation, the fundamental role of serotonin (5-HT) in enteric neuroimmune mechanisms, and future perspectives are reviewed.
Systemic administration of the bifunctional opioid/neuropeptide FF receptors agonist BN‐9 produced peripheral antinociception in preclinical mouse models of pain
It is suggested that systemic injection of BN‐9 causes effective antinociception in different preclinical pain models via the peripheral opioid receptors, providing an attractive approach to develop peripherally acting opioid analgesics with multiple targeting properties.
MAHMI database: a comprehensive MetaHit-based resource for the study of the mechanism of action of the human microbiota
The Mechanism of Action of the Human Microbiome (MAHMI) database is a unique resource that provides comprehensive information about the sequence of potential immunomodulatory and antiproliferative


Emerging receptor target in the pharmacotherapy of irritable bowel syndrome with constipation
The evidence base supporting the role of guanylate cyclase C (GC-C) activation in the modulation of gastrointestinal transit and, in particular, in visceral hypersensitivity is described.
Current and Emerging Pharmacotherapeutic Options for Irritable Bowel Syndrome
This review will focus on randomized controlled trials with a general uniformity in study design, a rigorous patient selection and appropriate treatment durations, which may prove promising in treating patients with irritable bowel syndrome.
Irritable bowel syndrome: the role of food in pathogenesis and management.
Although many patients with IBS adopt any one of a host of dietary changes in an attempt to alleviate their symptoms, there has been, until recently little scientific basis for any dietary recommendation in IBS.
The safety of novel drugs used to treat irritable bowel syndrome
Introduction: Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder with a high prevalence. Besides efficacy, the safety of each drugs used to treat GI disorders is an important
Current and future pharmacological treatments for diarrhea-predominant irritable bowel syndrome
Greater understanding of the mechanisms in IBS-D has led to promising approaches to develop more efficacious therapies, and opportunities to address unmet needs are addressed.
Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds.
  • M. Callahan
  • Medicine
    Journal of clinical gastroenterology
  • 2002
Loperamide, a mu (mu) opioid receptor agonist, is safe and effective for IBS patients with diarrhea (IBS-D) as the predominant bowel syndrome, and selective antagonists for neurokinin receptors type 1 and type 2 show promise in reducing gut motility and pain.
Pharmacologic Therapy for the Irritable Bowel Syndrome
  • N. Talley
  • Medicine
    American Journal of Gastroenterology
  • 2003
Tegaserod, a partial 5HT4 agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown.
Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome.
Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier and subsequent neuronal sensitization and/or activation in IBS.
Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.
How pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS is discussed.
The quest for biomarkers in IBS—where should it lead us?
The current literature concerning the proposed biomarkers including those of altered gut motility, of visceral hypersensitivity, of abnormal brain mechanisms, of serum, fecal and mucosal inflammation and of increased intestinal permeability are reviewed.