DOPAMINE TARGETING DRUGS FOR THE TREATMENT OF SCHIZOPHRENIA: CURRENT TREATMENT, DEVELOPMENT OF ANTIPSYCHOTICS, COMPARISON OF ANTIPSYCHOTICS

Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the world’s population. This disease is associated with considerable morbidity, placing a major financial burden on society. Antipsychotics have been the mainstay of the pharmacological treatment of schizophrenia for decades. The traditional, typical and atypical antipsychotics demonstrate clinical efficacy in treating positive symptoms, such as hallucinations and delusions, while they are largely ineffective and may worsen negative symptoms, such as blunted affect and social withdrawal, as well as cognitive function. The inability to treat these latter symptoms may contribute to social function impairment associated with schizophrenia. The dysfunction of multiple neurotransmitter systems in schizophrenia suggests that drugs selectively targeting one neurotransmission pathway are unlikely to meet all the therapeutic needs of this heterogeneous disorder. However, unintended engagement of multiple pharmacological targets, or excessive engagement of intended targets, can lead to adverse effects and poor tolerability. In this article, we will review marketed typical and atypical antipsychotics and new therapeutic agents targeting dopamine receptors and other neurotransmitters for the treatment of schizophrenia. Representative typical and atypical antipsychotic drugs, as well as new investigational drug candidates, will be systematically reviewed and compared with respect to structure-activity relationships, pharmacokinetic properties, drug metabolism and safety, pharmacological properties, preclinical data in animal models, clinical outcomes, and associated side effects.