Molecular biological perspectives in treating neuropsychiatric disorders with dopaminergic drugs

This review aims to present perspectives of molecular neuropharmacology in the development of more targeted drugs that modulate dopaminergic functions in various neuropsychiatric disorders. Recent advances in molecular neurobiology have revealed five distinct dopamine receptor (DR) genes and multiple allelic variations encoding DR subtypes with functional diversity. Depending on the different biophysical and pharmacological properties and the various cerebral distributions of the DR subtypes, the action profile of subtype-specific dopaminergic drugs can be predicted. In vitro expression of DR gene variants in mammalian cell lines will facilitate the screening and pharmacological characterization of dopaminergic ligands. Molecular modeling of the DR subtypes by three-dimensional computer models will be useful for establishing structure-function relationships between ligands and the DRs, and could provide a template for the design of receptor-specific drugs. In the near future, drugs modulating dopamine turnover and transport or involving the successive effector systems will increase the current therapeutical spectrum.