Based on the pharmacophore information and the analysis of structure–activity relationship of SSRIs and SNRIs, a series of substituted aromatic heterocyclic arylamidine derivatives were designed and   synthesized in order to search for lead compounds with dual activity.  All of them were new compounds, and their structures were confirmed by ¹H NMR and HRMS.  Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibitory activity and some compounds exhibited NE reuptake  inhibitory activity.  These aromatic heterocyclic arylamidine designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.