Muscarinic receptors in psychiatric disorders - can we mimic 'health'?

The concept that acetylcholine is involved in the pathophysiologies of psychiatric disorders has existed since the 1950s. There is very strong evidence implicating a dysfunctional muscarinic system in schizophrenia, +with less information available for bipolar disorder and major depressive disorder. The translation of this evidence into clinically viable treatments has been disappointing; hampered by problems associated with developing drugs that target the requisite members of the muscarinic family, rather than all of the receptors, which results in unacceptable side-effect profiles. The discovery of additional binding sites, other than the one occupied by acetylcholine, has revitalised research into this aspect of psychopharmacology. New compounds are now being developed that have the potential to selectively target individual muscarinic receptors in the central nervous system. The question that remains to be answered is whether stimulating central muscarinic receptors will result in the reestablishment of normal central muscarinic activity? The purpose of this review is to (i) summarise the data supporting a role of the muscarinic system in schizophrenia, bipolar disorder and major depressive disorder, and (ii) give an overview of some of the new selective muscarinic ligands that are currently in development and try to address the issue of re-establishing appropriate central muscarinic function.