Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets

Abstract

SUMMARYPhylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents.

The muscarinic system, cognition and schizophrenia

“…With increasing effort being directed towards developing new drugs to treat the cognitive symptoms of schizophrenia, it would be reasonable to suggest recommencing research on a drug that has already shown therapeutic efficacy. Scarr (2012Scarr ( , 2013, Wess et al (2003), Wezenberg et al (2005). …”

Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

“…The cholinergic M2 receptor gene belongs to a family of muscarinic acetylcholine G-protein coupled receptors with five known subtypes (M1–M5). The M2 receptors in the mesolimbic dopaminergic system play a significant role in modulating the level of dopamine release (Picciotto et al, 2012; Scarr, 2012; Cachope et al, 2012; Oldenburg and Ding, 2011; Witten et al, 2010). This has a important effect in governing the reward system (Mark et al, 2011; Shabani et al, 2010), including modulating the effects of alcohol on it (Adermark et al, 2011).…”

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

“…The cholinergic system in the brain is comprised primarily of nicotinic acetylcholine receptors (nAChRs; Paterson and Nordberg, 2000; Kalamida et al, 2007) and muscarinic acetylcholine receptors (mAChRs; Scarr, 2012; Thiele, 2013), members of the cys-loop superfamily of ligand gated ion channels and G protein-coupled receptors, respectively. Dysregulation of both mAChRs and nAChRs have been strongly associated with several neurological disorders (Janowsky et al, 1972; Freedman et al, 1995; Warpman and Nordberg, 1995; Breese et al, 2000; Salamone and Zhou, 2000; Perry et al, 2001; Woodruff-Pak and Gould, 2002; Ray et al, 2005; Quik et al, 2007; Scarr, 2012).…”

“…Dysregulation of both mAChRs and nAChRs have been strongly associated with several neurological disorders (Janowsky et al, 1972; Freedman et al, 1995; Warpman and Nordberg, 1995; Breese et al, 2000; Salamone and Zhou, 2000; Perry et al, 2001; Woodruff-Pak and Gould, 2002; Ray et al, 2005; Quik et al, 2007; Scarr, 2012). …”