Novel approaches to drug design for the treatment of schizophrenia

Schizophrenia is an important health issue affecting almost 1% of the population with significant unmet medical needs. The classical drug targets for the treatment of schizophrenia are dopamine D2 receptors. Second-generation ('atypical') drugs block more receptors of the G-protein-coupled receptor (GPCR) class 1 (e.g., clozapine is a D(2)-5HT(2) antagonist).

In this article, the author presents the new targets for GPCR as well as ligand-gated ion. Furthermore, the author reviews the opportunities for drug design offered by the structures solved recently.

For drug design, the availability of these protein structures, or the possibility to build high quality models, allows to shift the paradigm from ligand-based to target-based drug design. The analysis of the drugs, both on the market and in development, shows that numerous targets are being considered which may reveal an ambiguity on the ideal drug target. This situation may be simplified, in the future, owing to recent integrative projects: the 'Human Brain Project' and the 'Brain Activity Map' that aim at modeling the brain as well as the Allen Atlas.