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S1RA + NMDAE is an investigational combination therapy comprising S1RA, a highly selective sigma-1 receptor (σ1R) antagonist, and an NMDA enhancer (NMDAE). This dual-modulation approach targets both the sigma-1 receptor and the N-methyl-D-aspartate receptor (NMDAR) system. S1RA acts by antagonizing σ1R, which modulates NMDAR function through protein-protein interactions; this can influence glutamatergic neurotransmission implicated in neuropsychiatric disorders. The addition of an NMDA enhancer aims to further potentiate NMDAR activity. The combination is being studied for treatment-resistant schizophrenia, with the rationale that simultaneous modulation of these pathways may address glutamate hypofunction associated with psychosis[1][2].
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