Recent advances in pharmacological research on the management of irritable bowel syndrome

摘要

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder, is associated with various factors, including lifestyle, infection, stress, intestinal flora, and related diseases. The pharmacotherapeutic stimulation of receptors and downstream signaling pathways is effective in reducing IBS symptoms; however, it is still associated with adverse effects. Various receptors related to GI motility and visceral hypersensitivity should be considered to enhance the benefit/risk ratio of IBS treatments. This review discusses recent pharmacological advances in IBS management. Several receptors related to GI motility and abdominal pain are investigated in various angles. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter that activates the colonic mucosal 5-HT~(4)receptor without causing severe cardiovascular adverse effects. The clinical potential of ramosetron for diarrhea-predominant IBS has been suggested because of a lower risk of ischemic colitis than conventional 5-HT~(3)receptor antagonists. Toll-like receptors (TLRs), especially TLR2 and TLR4, show a significant effect on the post-infection symptoms and lipopolysaccharide-mediated regulation of GI motility. Histamine is a well-known nitrogenous compound that regulates inflammatory responses and visceral hypersensitivity. Histamine 1 receptor-mediated sensitization of the transient receptor potential vanilloid 1 is associated with IBS. Pharmacological approaches based on these signaling pathways could be useful in the development of novel IBS treatments.