Advances in the study of NMDA receptors in depression pathogenesis and the antidepressant efficacy of their antagonists.
Asian journal of psychiatry June 1, 2025 Mingrui Chen, Jingyan Jin, Hongsheng Bi et al. 12 citations
NMDA receptors, a type of glutamate receptor, are central to neuroplasticity and are implicated in depression, where their dysfunction can cause neuronal damage and disrupt brain adaptability. Ketamine, an NMDA receptor antagonist, rapidly alleviates severe depression and suicidal thoughts within hours by reducing NMDA receptor activity and activating the mTOR pathway, but its use is limited by side effects like hallucinations and dependency. Esketamine, an FDA-approved variant, offers improved efficacy and fewer side effects. Other NMDA-modulating compounds, including memantine and rapastinel, are under investigation. Future research should focus on NMDA receptor molecular mechanisms to develop safer, more effective, and personalized depression treatments with longer-lasting effects.