ibodutant and octylonium

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT

Topics: Abdominal Pain; Anti-Infective Agents; Antidepressive Agents; Butyrophenones; Dipeptides; GABA Agents; Gastrointestinal Agents; Histamine H1 Antagonists; Humans; Imidazoles; Irritable Bowel Syndrome; Mentha piperita; Parasympatholytics; Phenylalanine; Piperidines; Plant Oils; Probiotics; Quaternary Ammonium Compounds; Rifamycins; Rifaximin; Serotonin 5-HT3 Receptor Antagonists; Thiophenes; Visceral Pain

The present aim was to study the modulation of NK2 receptor internalization by two compounds, the spasmolytic otilonium bromide (OB) endowed with NK2 receptor antagonistic properties and the selective NK2 receptor antagonist ibodutant.. Full-thickness human colonic segments were incubated in the presence of OB (0.1-10 μmol L(-1)) or ibodutant (0.001-0.1 μmol L(-1)), with or without the NK2 receptor selective agonist [ßAla8]NKA(4-10) and then fixed in 4% paraformaldehyde. Cryosections were processed for NK2 receptor immunohistochemical revelation. Quantitative analysis evaluated the number of the smooth muscle cells that had internalized the NK2 receptor.. Immunohistochemistry revealed that in basal condition, the NK2 receptor was internalized in about 23% of total smooth muscle cells. The exposure to the selective NK2 receptor agonist induced internalization of the receptor in more than 77% of the cells. Previous exposure to both OB or ibodutant, either alone or in the presence of the agonist, concentration-dependently reduced the number of the cells with the internalized receptor.. Both OB and ibodutant antagonize the internalization of the NK2 receptor in the human colon. As NK2 receptors are the predominant receptor mediating spasmogenic activity of tachykinins on enteric smooth muscle, we hypothesize that the antagonistic activity found for both OB and ibodutant should play a specific therapeutic role in gut diseases characterized by hypermotility.

Topics: Adult; Aged; Aged, 80 and over; Animals; Colon; Dipeptides; Female; Gastrointestinal Agents; Humans; Immunohistochemistry; Male; Middle Aged; Quaternary Ammonium Compounds; Receptors, Neurokinin-2; Thiophenes