Neuropharmacological targets for schizophrenia treatment: An update

Schizophrenia is a severe chronic psychiatric disorder that affects around 24 million people worldwide. It is characterized by a combination of positive (such as hallucinations and delusions), negative (including asociality, alogia, and avolition), and cognitive symptoms (implicating attention, memory, and executive functions). These symptoms contribute to significant personal, social and occupational impairments, substantially affecting the patients' quality of life. The etiology of schizophrenia is multifactorial, involving both genetics and environmental factors, with strong evidence supporting a neurodevelopmental origin. Additionally, schizophrenia pathophysiology has been associated with dysregulations in several systems, including the dopaminergic, glutamatergic and purinergic systems, and a chronic neuroinflammatory process. These findings reinforce that this condition is most likely the result of a complex relationship between biological, environmental, and neurochemical factors. Current pharmacological treatment remains focused on dopaminergic activity, particularly through the use of antipsychotics. However, both the glutamatergic and purinergic systems have been explored as possible therapeutic targets and have presented themselves as promising alternatives. In addition, the interaction between all these neurochemical systems in the context of schizophrenia has been poorly reported. Here, we provide a perspective of the dopaminergic, glutamatergic, and purinergic pathways integration, contributing to schizophrenia pathophysiology, suggesting potential targets for pharmacological approaches.