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

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.

Effects of buspirone on dopamine dependent behaviours in rats.

Buspirone, a partial agonist of 5-hydroxytryptamine autoreceptors, selectively blocks presynaptic nigrostriatal D2 dopamine (DA) autoreceptors. At doses which antagonised action of apomorphine in biochemical presynaptic nigrostriatal D2 DA autoreceptor test systems buspirone neither induced catalepsy nor antagonised apomorphine-induced turning behaviour in rats indicating that at these doses buspirone does not block postsynaptic striatal D2 and D1 DA receptors. This study determines whether at high doses buspirone blocks postsynaptic striatal D2 and D1 DA receptors and provides behavioural evidence for selective blockade of presynaptic nigrostriatal D2 DA autoreceptors by smaller doses of buspirone. We investigated in rats whether buspirone induces catalepsy and effect of its pretreatment on DA agonist induced oral stereotypies and on cataleptic effect of haloperidol and small doses (0.05, 0.1 mg/kg, ip) of apomorphine. Buspirone at 1.25, 2.5, 5 mg/kg, ip neither induced catalepsy nor antagonised apomorphine stereotypy but did potentiate dexamphetamine stereotypy and antagonised cataleptic effect of haloperidol and small doses of apomorphine. Buspirone at 10, 20, 40 mg/kg, ip induced catalepsy and antagonised apomorphine and dexamphetamine stereotypies. Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore, buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors, increases synthesis of DA and makes more DA available for release by dexamphetamine and during haloperidol-induced compensatory 'feedback' increase of nigrostriatal DAergic neuronal activity and thus potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.