The (S)-isomer of [³H]zacopride labels 5-HT₃ receptors with high affinity in rat brain

The distribution of 5-HT₃ receptor sites was examined in rat brain by aautoradiography using ³H-enantiomers of zacopride. The (S)-³H-isomer labelled high densities of binding sites in the hippocampus, amygdala and cortex. The (R)-³H-isomer labelled considerably fewer sites than the (S)-isomer in nuclei of the lower medulla and did not exhibit any specific binding in the forebrain. These differences confirm that the (S)-isomer is specific for 5-HT₃ binding sites and that it has a higher affinity than the (R)-isomer at these sites. These results are not consistent with the notion that 5-HT₃ antagonist activity explains the anxiolytic effects of zacopride.