Figure 1. Putting a bias into antipsychotics. A team from The University of North Carolina at Chapel Hill and Duke University has designed a class of antipsychotic compounds called b-arrestin-biased ligands that could have a better therapeutic index than existing drugs to treat schizophrenia and other neuropsychiatric disorders.

Using the antipsychotic drug Abilify as a synthetic scaffold, the researchers designed a biased agonist that bound the dopamine D2 receptor [a] and activated downstream signaling through the b-arrestin pathway [b] without agonizing G protein-mediated pathways [c]. In mice, the compound showed antipsychotic effects without triggering neurological side effects.

Abilify aripiprazole is marketed by Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. Ltd. to treat depression, bipolar disorder and schizophrenia.