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Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents

Molecular Psychiatry volume 7, pages S57–S63 (2002)Cite this article

Abstract

The evidence for the involvement of cholinergic muscarinic receptors in mania and depression is reviewed. Small pilot trials with cholinesterase inhibitors and muscarinic agonists suggest that stimulation of muscarinic receptors may produce an antimanic effect, possibly by activation of muscarinic M4 receptors. It is concluded that it is not likely that currently used mood stabilizers, such as lithium, valproic acid and carbamazepine, work directly through muscarinic receptor mechanisms. Furthermore, the evidence indicates that antipsychotic agents used for mania are working through the common mechanism of antagonism of dopamine D2 receptors, and interactions with muscarinic receptors do not play a key role. Finally, it is hypothesized that olanzapine has robust antimanic activity, due to blockade of dopamine D2 receptors and antagonism of other monoaminergic receptors. Olanzapine may normalize mood due to antidepressant-like activities, such as 5-HT2A receptor antagonism and increasing cortical norepinephrine and dopamine.

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  1. Neuroscience Research Division, Lilly Research Laboratories, Indianapolis, IN, USA

    F P Bymaster & C C Felder

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Bymaster, F., Felder, C. Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents. Mol Psychiatry 7 (Suppl 1), S57–S63 (2002). https://doi.org/10.1038/sj.mp.4001019

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