The antidepressant-like effect and proposed mechanism of action of TPN672MA, a novel serotonin-dopamine receptor modulator for the treatment of schizophrenia

TPN672MA, an innovative antipsychotic drug candidate currently in clinical trials, acts as a dopamine D₂/D₃ receptor partial agonist, serotonin 5-HT_1A receptor agonist, and serotonin 5-HT_2A receptor antagonist. Preclinical investigations have demonstrated its potential in treating the core symptoms of schizophrenia. The present study highlights TPN672MA’s significant antidepressant-like effects in classical behavioral models, such as the chronic social defeat stress paradigm. The pronounced 5-HT_1A receptor agonism and D₂/D₃ receptor partial agonism of TPN672MA likely contribute to its therapeutic effects in depression. Additionally, TPN672MA’s antidepressant-like efficacy may be linked to its ability to enhance the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD95) in the hippocampus. Furthermore, TPN672MA displayed a more rapid onset of antidepressant-like action. In conclusion, TPN672MA represents a promising new drug candidate for the treatment of symptoms of schizophrenia and depression.