Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents.
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 M(4) 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 D(2) 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 D(2) receptors and antagonism of other monoaminergic receptors. Olanzapine may normalize mood due to antidepressant-like activities, such as 5-HT(2A) receptor antagonism and increasing cortical norepinephrine and dopamine.
Bymaster
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Neuroscience Research Division, Lilly Research Laboratories, Indianapolis, IN 46285-0510, USA. f.bymaster@lilly.com
Felder
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CC
D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D006801:Humans; D018721:Muscarinic Agonists / Q000627:therapeutic use*; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D014150:Antipsychotic Agents; D018721:Muscarinic Agonists; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic