Effect of itopride hydrochloride on the ileal and colonic motility in guinea pig in vitro.
OBJECTIVE
Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs.


METHODS
The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10 cm with 2-cm intervals.


RESULTS
In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6) M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9) M). Dopamine (10(-8) M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6) M). Dopamine (10(-8) M) delayed colonic transit time that was also recovered after infusion of itopride.


CONCLUSIONS
Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.
Lim
Hyun Chul
HC
Department of Internal Medicine, Yonsei University College of Medicine, 612 Eonjuro, Gangnam-gu, Seoul 135-720, Korea.
Kim
Young Gyun
YG
Lim
Jung Hyun
JH
Kim
Hee Sun
HS
Park
Hyojin
H
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009388:Neostigmine / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology
D001549:Benzamides; D001593:Benzyl Compounds; D002800:Cholinesterase Inhibitors; D017447:Receptors, Dopamine D1; D009388:Neostigmine; C102254:itopride; D004298:Dopamine