Mitemcinal (GM-611), an orally active motilin agonist, facilitates defecation in rabbits and dogs without causing loose stools.
The effects of mitemcinal (GM-611), an orally active motilin agonist, on defecation were investigated in rabbits and dogs. In normal rabbits, within 0-3 h of dosing, orally administered mitemcinal (2.5-10 mg kg(-1)) increased stool weight in a dose-dependent manner without causing loose stools. Sennoside (12-48 mg kg(-1)) also facilitated defecation within 2-9 h of oral administration, but the stools were significantly loosened. In the morphine-induced constipation model, the stool weight of morphine-treated rabbits (1 mg kg(-1)) was only 37.5% of that of untreated animals. Mitemcinal (0.5-20 mg kg(-1)) dose-dependently increased stool weight without increasing stool water content. At the highest dose of mitemcinal, stool weight recovered to 83.9% of that of untreated animals. In normal dogs, mitemcinal (0.3-3 mg kg(-1)) reduced the time to first bowel movement after oral administration without inducing diarrhoea at any dose. These results indicate that mitemcinal facilitates defecation without inducing severe diarrhoea. It is suggested that mitemcinal may be a novel therapeutic agent for constipation that enables easier control of the timing of defecation because of the early onset and short duration of its action, compared with sennoside.
Sudo
H
H
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Gotemba, Shizuoka, Japan.
Ozaki
K
K
Muramatsu
H
H
Kamei
K
K
Yogo
K
K
Cynshi
O
O
Koga
H
H
Itoh
Z
Z
Omura
S
S
Takanashi
H
H
D000818:Animals; D003248:Constipation / Q000139:chemically induced; D003672:Defecation / Q000187:drug effects / Q000502:physiology; D003967:Diarrhea / Q000517:prevention & control; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology; D009037:Motilin / Q000819:agonists*; D011817:Rabbits; D012016:Reference Values
D005765:Gastrointestinal Agents; D009037:Motilin; D004917:Erythromycin; C103741:mitemcinal; D009020:Morphine