Experimental Serotonergic Agents for the Treatment of Schizophrenia

Schizophrenia remains one of the most chronic and highly disabling mental disorder. To date, the pathomechanism of schizophrenia is not fully understood and current treatments are characterized by some limitations. First- and second-generation antipsychotics have shown clinical efficacy in treating positive symptoms, while are poorly effective on both negative symptoms and cognitive deficits. Moreover, they can involve many metabolic and neurological side effects, leading to low therapeutic compliance. Many evidence suggested that serotonin may play a complex role in the neurobiology of schizophrenia. Therefore, new drugs targeting 5-HT receptors (5-HTRs) have become an important area of research in schizophrenia in the hope that treatment efficacy may be improved without inducing side effects observed with currently available antipsychotics. Research using the main database sources was conducted to obtain an overview of preclinical and clinical pharmacological 5-HTR-targeted therapies in patients with schizophrenia. We identified 17 experimental serotonergic agents, under study for their potential use in schizophrenia treatment. Particularly, AVN-211, LuAF-35700 and Brilaroxazine are currently under clinical development. Moreover, some compounds showed some pro-cognitive and antipsychotic-like properties in animal models, while other agents showed contradictory effects in improving symptoms and were removed from the development program. Although some serotonergic drugs seem promising for improving the treatment of schizophrenia, further studies regarding the pathophysiological mechanisms of schizophrenia and novel compounds as well as high-quality trials are necessary in order to improve schizophrenia outcomes.