Striking the right balance between G_i and G_q signalling

A new study explains why some inhibitors of the serotonin G_q protein-coupled receptor 2AR (such as clozapine), but not others (such as ritanserin), have antipsychotic actions. The authors showed that 2AR can form a heteromeric complex with metabotropic glutamate receptor 2 (mGluR2) — which is a G_i protein-coupled receptor — and that this interaction can enhance glutamate-induced G_i signalling and reduce serotonin-induced G_q signalling. The intracellular G_i and G_q signalling balance is predictive of the anti- or pro-psychotic activity of drugs targeting 2AR and mGluR2, providing a potential new metric to improve current antipsychotic therapies.