In this study, we performed amino acid substitutions and structural optimization of VIpep-3 and successfully generated a derivative, KS-133, which possesses the following drug-like properties: 1) selective antagonistic activity against VIPR2 at the nanomolar level, 2) remarkable resistance to protease degradation, and 3) prevention of cognitive decline in a mouse model of psychiatric disorders by early postnatal activation of VIPR2. The gene discussed is VIPR2; the disease is Mental deterioration.