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.
The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside.
Hirabayashi
T
T
Pediatric Surgery, St Luke's International Hospital, Tokyo, Japan. thirabay@luke.or.jp
Morikawa
Y
Y
Matsufuji
H
H
Hoshino
K
K
Hagane
K
K
Ozaki
K
K
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D003672:Defecation / Q000187:drug effects*; D004285:Dogs; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D054368:Laxatives / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists*; D018013:Receptors, Neuropeptide / Q000819:agonists*; D012676:Senna Extract; D000081226:Sennosides; D014159:Transducers
D000880:Anthraquinones; D054368:Laxatives; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; D000081226:Sennosides; C050802:motilin receptor; D004917:Erythromycin; C103741:mitemcinal; D012676:Senna Extract