Depression is the major mental disorder and over one million patients are suffering from this disease. It was also reported that the number of patients showing resistance toward anti-depressant, i.g. SSRI and SNRI, got increase. We have already known that molecular mechanism underlying depression is heterogeneous so that it is hard to estimate the efficacy of anti-depressant without molecular rationale. Postmortem human brain analysis indicated that the number of AMPA receptors (AMPARs), major molecule controlling synaptic functions, varied among depression patients and the results of these analysis were not consistent. To clarify the dynamics of AMPARs in depression patients, we developed the novel PET imaging method to measure the density of AMPARs in depression patients. This result showed that depression patients decreased AMPARs broadly throughout the brain. This fact motivated us to develop novel AMPARs potentiator in order to cure the depression. To find the compound showing high affinity to AMPARs and high BBB penetratability, we modified the compound named PEPA, already known to bind specifically to AMPARs, and finally succeeded in synthesizing the seed compound. This compound could exert the anti-depressant effect quickly and sustained for a week after the cessation of drug administration. Furthermore, this anti-depressant effect was significantly stronger that another AMPARs potentiators.