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 autoradiography 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.
Waeber
C
C
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Pinkus
L M
LM
Palacios
J M
JM
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C055971:zacopride