Cisapride, a gastroprokinetic agent, binds to 5-HT₄ receptors

Abstract

The affinity of cisapride for 5-HT₄ receptors was investigated in comparison with those of other 5-HT₄ receptor agonists and antagonists, such as 5-HT, 5-MeOT, mosapride, zacopride, metoclopramide, BIMU8, GR113808, SDZ 205-557 and ICS 205-930. Cisapride and the other compounds dose-dependently inhibited specific ³H-GR 113808 binding to 5-HT₄ receptors in guinea pig striatal membranes, and complete inhibition of specific ³H-GR1 13808 binding was achieved at the high concentrations of these compounds. Cisapride was 1.9-, 7.3-, 4.3-, 11 and 26-fold more potent than 5-HT, 5-MeOT, mosapride, zacopride and metoclopramide, respectively, in competing for 5-HT₄ receptors. To determine the manner of interaction between cisapride and 5-HT₄ receptors, Scatchard analysis of ³H-GR113808 specific binding to striatal membranes was performed. Cisapride increased the Kd value of ³H-GR 113808 in striatal membranes in a dose-dependent manner without any influence on the binding density (B_max) of ³H-GR1 13808. These findings indicate that cisapride binds to 5-HT4 receptors competing with ³H-GR 113808 in guinea pig striatal membranes.