Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo.
We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.
Pharmacology Laboratory, GPRD Discovery, Abbott Japan. Japan. tadashi.tsubouchi@abbott.com
Tadashi
T
Tsubouchi
Takaharu
T
Saito
Fujie
F
Mizutani
Toshie
T
Yamauchi
Yuji
Y
Iwanaga
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005746:Gastric Emptying / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats
D001549:Benzamides; D001593:Benzyl Compounds; C102254:itopride