Dopamine D3 Receptors: From Bench to Bedside.

Dopamine D3 receptors belong to the dopamine D2-like receptor family, which also includes D2 and D4 receptors. These receptors have limited anatomical distribution and are mainly expressed in brain regions and pathways that typically mediate the actions of antipsychotic drugs and medication used against Parkinson's disease (PD). The development of cariprazine, the fi rst D2/D3 partial agonist with prominent affi nity and preferential activity at D3 receptors over other dopamine receptor subtypes was a landmark that provided new insights into the neurochemical and physiological functions of D3 receptors. Preclinical studies and clinical trials provided evidence for the clinical advantages of cariprazine in the treatment of schizophrenia and bipolar disorder. Cariprazine became the fi rst antipsychotic drug approved for the treatment of manic, mixed and depressive episodes in bipolar I disorder. Antagonism of D3 receptors may play a role in ameliorating symptoms of levodopa-induced dyskinesia and psychosis in PD patients treated with levodopa/carbidopa. Accordingly, D3 receptors constitute attractive targets for developing novel drugs for the improved treatment of different psychiatric and neurological disorders. (Neuropsychopharmacol Hung 2021; 23(2): 272-280).