N-methyl-D-aspartate (NMDA) receptors are considered to be one of the most promising targets for treatment-resistant depression. The majority of known ligands may cause undesirable side-effects, except tetrapeptide rapastinel which demonstrated rapid antidepressant effect without psychotomimetic side effects. High shape similarity was noticed between dipeptide Phe-Tyr and NMDA receptor non-competitive antagonist ifenprodil which imply the possibility for antagonistic action of this peptide. A series of analogs were selected based on the docking results and molecular dynamics simulations. A dipeptide D-Phe-L-Tyr showed modest inhibitory activity comparable to rapastinel.