Muscarinic Receptor Pharmacology and Circuitry for the Modulation of Cognition

摘要: The muscarinic cholinergic system constitutes an important part of the neuronal circuitry that modulates normal cognition. Muscarinic receptor antagonists are well known to produce or exacerbate impairments in attention, learning, and memory. Conversely, both direct-acting agonists indirect-acting agonists, such as acetylcholinesterase inhibitors, have shown cognition-enhancing properties, including improvements cognitive function, reversal deficits induced by antagonists, attenuation psychiatric neurological disorders, Alzheimer’s disease schizophrenia. However, until recently, lack small molecule ligands antagonize activate specific acetylcholine (mAChR) subtypes with high selectivity has been a major obstacle defining relative contributions individual mAChRs different aspects function for development novel therapeutic agents. These limitations may be potentially overcome recent discovery mAChR subtype-selective compounds, notably allosteric positive modulators, which exhibit greater than previous orthosteric agonists. In preclinical studies, these promising efficacy several models enhancement this chapter, we will review pharmacology relevant modulation cognition animals clinical populations.