Abstract We studied the relationships between electronic structure and 5-HT1A receptor binding affinity of a group of 2,5-dimethoxyphenethylamines and their N-2-methoxybenzyl-substituted analogs. The novelty of this study is that we analyzed four hypothesis about the mode of binding, leading to four different common skeletons. For all cases statistically significant equations were obtained, each one leading to a partial interaction pharmacophore. The integration of all the results into a unique pharmacophore that provides more detailed information about the mode of binding of these molecules to the 5-HT1A receptor.