New Antipsychotic Mechanism Discovered

PET scanIt has been estimated that as many as 50 million people worldwide suffer from schizophrenia and many of these will be treated with antipsychotic medicines. The so-called typical antipsychotics have been available since the mid-1950s and a number of newer agents, the atypical antipsychotics, have been introduced since 1990. Increased dopaminergic activity is thought to be a contributory factor in schizophrenia and all of the antipsychotic medicines interact with the dopamine D2 receptor although they have different affinities and modulate the receptor in different ways.

A new study has shown that, regardless of their effect on G-protein coupled signalling via the D2 receptor, antipsychotic drugs potently antagonize the dopamine-mediated interaction of the D2 receptor with β-arrestin-2.

Arrestins are proteins that were initially found to regulate signal transduction by silencing GPCRs, although they have recently been shown to directly activate signalling pathways. The new results suggest that selective targeting of the interaction of D2 with β-arrestin-2 may provide a new opportunity for the development of antipsychotic medicines. More generally, targeting β-arrestin signalling pathways may open opportunities in other therapeutic areas.