“Schizophrenia is a disorder that involves hallucinations, delusions and cognitive impairment, and that affects nearly 1% of the global population. The mainstays of therapy have been drugs that block the activity of the D2 dopamine receptor (D2R), a member of the large G-protein-coupled receptor (GPCR) superfamily of membrane proteins. Unfortunately, most of these antipsychotic drugs come with a plethora of debilitating side effects, many of which are due to off-target interactions with other GPCRs. In a paper in Nature, Wang et al. now report the crystal structure of D2R in complex with the antipsychotic drug risperidone. The structure reveals features that might be useful for the design or discovery of drugs that have greater selectivity for D2R than existing therapeutics, and consequently have fewer side effects….”
Sibley DR and Shi L: A new era of rationally designed antipsychotics. Nature (News and Views, February 26, 2018).