New Treatment Targets to Improve Symptoms in Schizophrenia

Current antipsychotic medications (which focus on antagonism or partial agonism at the dopamine D2 receptor and antagonism at the serotonin 5-HT2A receptor) typically alleviate positive symptoms, but negative and cognitive symptoms often persist in patients with schizophrenia and hinder their return to full functioning. Although strategies, such as combining antipsychotics and adding adjunctive agents to antipsychotics, have attempted to meet this treatment need, their effectiveness has been inadequate. However, a hypothesis based on the glutamate system’s effect on dopamine may explain the positive, negative, and cognitive symptoms of schizophrenia. Therapeutic agents that target the glutamate system are being investigated, including adjunctive agents that bind to sites on N-methyl-D-aspartate (NMDA) receptors (glycine, D-serine, D-cycloserine) and adjunctive glycine reuptake inhibitors (sarcosine and bitopertin), as well as agents that work through different pathways, such as α-7 nicotinic acetylcholine receptor agonism (encenicline).

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