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• W2100265358 abstract "Background. The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia. Aims. To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract. Materials and methods. Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations. Results. Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT3 receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine. Conclusions. Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect." @default.
• W2100265358 created "2016-06-24" @default.
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• W2100265358 date "2003-04-01" @default.
• W2100265358 modified "2023-09-27" @default.
• W2100265358 title "5-HT4 Receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract" @default.
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• W2100265358 doi "https://doi.org/10.1016/s1590-8658(03)00061-6" @default.
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