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Schizophrenia is a complex disorder characterized by psychosis, as well as behavioural, cognitive and social deficits. Current antipsychotic treatments — which primarily antagonize the D2 dopamine receptor — reduce psychotic symptoms, but are less effective against other symptoms and are associated with a multitude of adverse effects. Muscarinic acetylcholine receptor (mAChR) agonists have emerged as a promising alternative to dopamine receptor-based therapies. Here, Burger et al. explore the molecular pharmacology of a potential first-in-class antipsychotic, xanomeline, a M4 mAChR agonist currently in phase III trials.