Functional group interactions of a 5-HT3R antagonist

Background  

Lerisetron, a competitive serotonin type 3 receptor (5-HT₃R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT₃R binding site. Site directed mutagenesis studies of the 5-HT_3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site.