Pre-clinical models, postmortem and neuroimaging studies all support a role for
muscarinic receptors in the molecular pathology of
schizophrenia. From these data it was proposed that activation of the
muscarinic M1 and/or M4 receptor would reduce the severity of the symptoms of
schizophrenia. This hypothesis is now supported by results from two clinical trials which indicate that activating central
muscarinic M1 and M4 receptors can reduce the severity of positive, negative and
cognitive symptoms of the disorder. This review will provide an update on a growing body of evidence that argues the
muscarinic M1 and M4 receptors have critical roles in CNS functions that are dysregulated by the pathophysiology of
schizophrenia. This realization has been made possible, in part, by the growing ability to visualize and quantify
muscarinic M1 and M4 receptors in the human CNS using molecular neuroimaging. We will discuss how these advances have provided evidence to support the notion that there is a sub-group of patients within the syndrome of
schizophrenia that have a unique molecular pathology driven by a marked loss of
muscarinic M1 receptors. This review is timely, as drugs targeting
muscarinic receptors approach clinical use for the treatment of
schizophrenia and here we outline the background biology that supported development of such drugs to treat the disorder.