Mitemcinal (GM‐611), an orally active motilin agonist, facilitates defecation in rabbits and dogs without causing loose stools

Abstract

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.

GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility

“…In conscious rabbits, erythromycin has been shown to increase both colonic motility and defecation, 35 most likely via activation of the motilin receptor, known to be present in the region of the rabbit intestine 36 . Further, the motilin receptor agonist mitemcinal has been reported to accelerate defecation both in untreated rabbits and dogs and after treatment of rabbits with a dose of morphine which induced constipation 37 . The present experiments with erythromycin 10 mg kg −1 i.v.…”

“…36 Further, the motilin receptor agonist mitemcinal has been reported to accelerate defecation both in untreated rabbits and dogs and after treatment of rabbits with a dose of morphine which induced constipation. 37 The present experiments with erythromycin 10 mg kg )1 i.v. confirm this type of activity and in addition, when dosed at 5 mg kg )1 i.v., show that GSK962040 can also significantly increase rabbit faecal output over a 2-h period.…”

Long‐term results of subtotal colectomy for acquired hypertrophic megacolon in eight dogs

“…The effect of mitemcinal (GM‐611), a novel orally active motilin agonist, on defecation has been investigated in rabbits and dogs. This compound has been shown to increase stool weight in a dose‐dependent fashion, without causing loose stools (Sudo and others 2007).…”

Stimulatory action of mitemcinal (GM‐611), an acid‐resistant non‐peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal‐induced giant migrating contractions during defecation in dogs

“…(K. Ozaki, unpublished data). Orally administered mitemcinal exhibits potent motility‐stimulating activity in the upper gastrointestinal tract of dogs and monkeys via the motilin receptor, 15,17 and it facilitates bowel movements in rabbits and dogs 18,19 . In a clinical trial, mitemcinal was shown to induce a significant response to treatment in diabetic gastroparesis, and patients who received mitemcinal experienced an increase in stool frequency in comparison with a placebo 16 …”

“…Orally administered mitemcinal exhibits potent motility-stimulating activity in the upper gastrointestinal tract of dogs and monkeys via the motilin receptor, 15,17 and it facilitates bowel movements in rabbits and dogs. 18,19 In a clinical trial, mitemcinal was shown to induce a significant response to treatment in diabetic gastroparesis, and patients who received mitemcinal experienced an increase in stool frequency in comparison with a placebo. 16 In the present study, we used mitemcinal to investigate the physiological role of motilin receptor agonists on colonic motility and assess the possibility of using mitemcinal for treatment of colonic motility disorders.…”