Serotonin Receptors as the Therapeutic Target for Central Nervous System Disorders

Abstract Because the serotonergic nervous system plays an important role in regulating diverse physiological functions including psychoemotional expression, sensorimotor integration, and cognitive functions, 5-hydroxytryptamine (5-HT) receptors are considered to be involved in the pathogenesis and treatment of various central nervous system (CNS) disorders. This article will review the diversity of 5-HT receptor functions in modulating CNS disorders and discuss the therapeutic potential of 5-HT receptors in the treatment of psychosis (e.g., schizophrenia), emotional disorders (e.g., anxiety and depression), and neurological diseases (e.g., Parkinson's disease). Existing evidence implies that stimulation of 5-HT 1A receptors or blockade of 5-HT 2 , 5-HT 3 , and 5-HT 6 receptors produces clinical benefits for the treatment of schizophrenia, such as an amelioration of negative symptoms, cognitive impairment, mood disturbances, and/or drug-induced extrapyramidal side effects. Stimulation of 5-HT 1A receptors and blockade of 5-HT 2 or 5-HT 3 receptors seem to be effective for the treatment of anxiety and depression. In addition, modulation of 5-HT 1A , 5-HT 2 , and 5-HT 3 receptors is also considered to be useful in the treatment of Parkinson's disease (e.g., improvement of parkinsonian motor symptoms, l -DOPA-induced dyskinesia and psychosis, and mood disturbances). Thus, new drugs acting on 5-HT receptor subtypes are expected to emerge as future therapy options for neuropsychiatry disorders. These therapeutic approaches modulating serotonergic activity may resolve the limitations of the current treatment of CNS disorders by improving clinical efficacy as well as reducing drug side effects.