Yonsei Med J.  2008 Jun;49(3):472-478. 10.3349/ymj.2008.49.3.472.

Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

• Lim HC
• Kim YG
• Lim JH
• Kim HS
• Park H

• KMID: 724264
• DOI: http://doi.org/10.3349/ymj.2008.49.3.472

Abstract

PURPOSE
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. MATERIALS AND 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 10cm 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. CONCLUSION: 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.

Keyword

Itopride; acetylcholinesterase inhibitor; dopamine D(2) receptor antagonist

MeSH Terms

Animals
Benzamides/*pharmacology
Benzyl Compounds/*pharmacology
Cholinesterase Inhibitors/pharmacology
Colon/*drug effects/physiology
Dopamine/pharmacology
Dose-Response Relationship, Drug
Gastrointestinal Motility/*drug effects
Guinea Pigs
Ileum/*drug effects/physiology
Neostigmine/pharmacology
Receptors, Dopamine D1/antagonists & inhibitors/physiology

Figure

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  Fig. 1 The effect of itopride on amplitude of peristaltic contraction. Itopride (10-10-10-6 M) did not change the amplitude of peristaltic contraction significantly.

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  Fig. 2 The effect of dopamine alone and itopride plus dopamine on amplitude of peristaltic contraction. Dopamine (10-8 M) or dopamine with itopride (10-7 M) did not change the amplitude significantly.

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  Fig. 3 Itopride (10-7 M) added to ACh (10-8 M) further increased the amplitude with no statistical significance.

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  Fig. 4 The effect of itopride on the propagation velocity of the peristaltic contraction. Itopride (10-10-10-6 M) significantly accelerated the velocity dose-dependently (*p < 0.05).

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  Fig. 5 The effect of dopamine alone and dopamine plus itopride on the propagation velocity of the peristaltic contraction. Dopamine (10-8 M) significantly decelerated the propagation velocity of the peristaltic contraction to 81.3 ± 5.4% (*p < 0.05). When itopride (10-7 M) was administered in the presence of dopamine, the velocity was increased up to 109 ± 3.86% with statistical significance (†p < 0.05).

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  Fig. 6 The effect of neostgmine on the propagation velocity of peristaltic contraction. Neostigmine at lower concentration significantly increased the velocity, but decreased at higher concentrations (*p < 0.05).

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  Fig. 7 The effect of itopride on the colonic transit time. Itopride (10-10-10-6 M) dose-dependently shortened colonic transit time (*p < 0.05).

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  Fig. 8 The effect of neostigmine on colonic transit time. Neostigmine (10-10-10-7 M) dose-dependently shortened colonic transit time (*p < 0.05).

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  Fig. 9 The effect of dopamine and dopamine plus itopride on colonic transit time. Dopamine (10-8 M) delayed colonic transit time up to 114.6 ± 9.3%. When itopride (10-7 M) was administered in the presence of dopamine, transit time was shortened to 80.1 ± 9.0% (†p < 0.05).

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  Fig. 10 ACh shortened colonic transit time but itopride together with ACh did not have an additive effect.

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