The effect of the selective 5-HT(3) receptor agonist on ferret gut motility.
The effect of the selective 5-hydroxytryptamine (5-HT)(3) receptor agonist YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate) on gut motility of fed ferrets was investigated. YM-31636 (0.1 mg/kg p.o.) induced a giant migrating contraction (GMC)-like, high-amplitude, ungrouped colonic contraction although it did not change the basal colonic motility pattern. This GMC-like contraction was always accompanied by defecation. Both GMC-like contraction and defecation were inhibited with the selective 5-HT(3) receptor antagonist ramosetron. YM-31636 affected gastric, duodenal and ileal motility pattern only slightly. These results suggest that 5-HT(3) receptor agonists such as YM-31636 are useful in treating constipation since they facilitate GMC-like contractions and defecation without undesired changes in gut motility pattern.
Nagakura
Yukinori
Y
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. nagakura@yamanouchi.co.jp
Kiso
Tetsuo
T
Miyata
Keiji
K
Ito
Hiroyuki
H
Iwaoka
Kiyoshi
K
Yamaguchi
Tokio
T
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003672:Defecation / Q000187:drug effects; D005289:Ferrets / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
C419869:2-(1H-imidazol-4-ylmethyl)-8H-indeno(1,2-d)thiazole; D001562:Benzimidazoles; D011758:Pyrroles; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C071315:ramosetron