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Based on radio-ligand binding and molecular modeling studies, sarpogrelate shows a moderate selectivity for 5-HT2B versus 5-HT2A receptors. To confirm the modeling data of sarpogrelate to 5-HT2B receptors predicting interaction of sarpogrelate towards Asp135 in helix 3 of 5-HT2B receptors, we constructed and characterized the mutation of this residue by site-directed mutagenesis. The Asp135Ala mutant did not exhibit any affinity for [3H]rauwolscine. Therefore, it was not possible to find sarpogrelate affinity to the mutant using [3H]rauwolscine. The mutation also abolished agonist-stimulated inositol phosphates formation. These results provide evidence that Asp135 is important for the interaction between 5-HT2B receptors and sarpogrelate. Keywords:: 5-HT2B receptor, sarpogrelate, site-directed mutagenesis