The high affinity of
antipsychotic drugs for the
dopamine D2 receptor focused attention onto the role of these receptors in the genesis of
psychoses and the pathology of
schizophrenia. However, psychotic symptoms are only one aspect of the complex symptom profile associated with
schizophrenia. Therefore, research continues into other neurochemical systems and their potential roles in key features associated with
schizophrenia. Modulating the
cholinergic system in attempts to treat
schizophrenia predates specific neurochemical hypotheses of the disorder.
Cholinergic modulation has progressed from the use of
coma therapy, through the use of
anti-cholinergic drugs to control side-effects of older (typical)
antipsychotic medications, to the development of drugs designed to specifically activate selected
muscarinic receptors. This review presents data implicating a decrease in
muscarinic receptors, particularly the M1 receptor, in the pathology of
schizophrenia and explores the potential physiological consequences of such a change, drawing on data available from
muscarinic receptor knockout mice as well as clinical and pre-clinical pharmacology. The body of evidence presented suggests that deficits in
muscarinic receptors are associated with some forms of
schizophrenia and that targeting these receptors could prove to be of therapeutic benefit to patients with the disorder.