title: Pharmacological profile of ramosetron, a novel therapeutic agent for IBS.
abstract: Ramosetron is a potent and selective serotonin (5-HT)(3) receptor antagonist that has been shown to affect abnormal colonic function and abdominal pain in animals. Ramosetron (0.3 to 100 microg/kg, p.o.) has been found to significantly suppress abnormal defecation induced by conditioned-fear stress (CFS), restraint stress, corticotropin releasing factor (CRF) and 5-HT in rats and mice, and these effects were more potent than those of alosetron, cilansetron or loperamide. On the other hand, ramosetron (3,000 microg/kg, p. o., once daily for 7 days) did not inhibit normal defecation in dogs while tiquizium significantly inhibited it. Ramosetron (3 to 100 microg/kg, p. o.) also significantly prevented CFS-induced acceleration of colonic transit and CRF-induced abnormal water transport in rats, respectively. Moreover, ramosetron (0.3 to 3 microg/kg, p. o.) significantly suppressed restraint stress-induced decrease in colonic pain threshold, an effect not observed with loperamide. These results indicate that ramosetron produce beneficial clinical effects on IBS symptoms.
authors.affiliation: Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. takuya.hirata@jp.astellas.com
authors.forename: T
authors.initials: T
authors.lastname: Hirata
authors.forename: T
authors.initials: T
authors.lastname: Funatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Keto
authors.forename: M
authors.initials: M
authors.lastname: Nakata
authors.forename: M
authors.initials: M
authors.lastname: Sasamata
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003672:Defecation / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy; D004285:Dogs; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D051379:Mice; D023421:Models, Animal; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; D012702:Serotonin Antagonists; C071315:ramosetron