Schizophrenia is a complex psychiatric disorder marked by positive, negative and cognitive symptoms, many of which are poorly addressed by current dopamine-blocking antipsychotics. Preclinical studies show that muscarinic acetylcholine M4 receptor positive allosteric modulators (M4 PAMs) can reduce hyperdopaminergic activity and improve both positive and negative symptom-related behaviors, suggesting they may offer enhanced antipsychotic efficacy with improved tolerability.