Muscarinic Myth Busters: Addressing Misconceptions of Muscarinic Receptor Activation in Schizophrenia

For decades, dopamine D2 receptor antagonism and partial agonism have defined the pharmacologic foundation of schizophrenia treatment. However, persistent negative symptoms, cognitive impairment, and treatment-limiting adverse effects underscore the need for mechanistically distinct approaches. Emerging therapies targeting muscarinic M1/M4 receptors represent a paradigm shift—challenging long-standing assumptions about receptor targets and expanding our understanding of cholinergic modulation in psychosis. This clinically focused session will critically examine common myths surrounding dopamine-centric treatment models and clarify the evolving role of muscarinic receptor activation in schizophrenia. Faculty will review the neurobiologic rationale for M1/M4 activation and present the latest clinical data on efficacy, tolerability, and safety from novel and investigational muscarinic agents. Particular attention will be paid to symptom domains affected, metabolic and extrapyramidal risk profiles, and practical considerations for integration into treatment algorithms. Participants will develop patient-centered strategies to optimize the use of muscarinic receptor activators, including appropriate patient selection, side-effect monitoring, and shared decision-making approaches. This session will equip clinicians with the knowledge and tools needed to thoughtfully incorporate emerging cholinergic therapies into contemporary schizophrenia care.

Supported by an educational grant from Bristol-Myers-Squibb.