Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs.
The prokinetic effects of mitemcinal, an orally active motilin receptor agonist, on the lower gastrointestinal tracts were investigated in conscious dogs. Oral administration of mitemcinal (0.1-1 mg/kg) stimulated colonic motility, which was measured by chronically implanted force-transducers, as well as gastric motility in a dose-dependent manner. The gastrointestinal contractile activities induced by mitemcinal were inhibited by the continuous intravenous infusion of GM-109, a selective motilin receptor antagonist. Oral administration of mitemcinal (0.3-3 mg/kg) also accelerated bowel movement after feeding without inducing diarrhea in dogs. The results demonstrate that mitemcinal stimulates colonic motility via motilin receptors and the effect of mitemcinal on colonic motility may reflect bowel movement after feeding. Thus, mitemcinal could be a promising agent for treatment of not only the upper but also the lower gastrointestinal motility disorders.
Ozaki
K
K
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Gotemba, Shizuoka, 412-8513, Japan.
Sudo
H
H
Muramatsu
H
H
Yogo
K
K
Kamei
K
K
Koga
H
H
Itoh
Z
Z
Omura
S
S
Takanashi
H
H
D000284:Administration, Oral; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D003672:Defecation / Q000187:drug effects*; D003967:Diarrhea; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009037:Motilin / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000187:drug effects*; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000187:drug effects*
D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; D004917:Erythromycin; C103741:mitemcinal