The specific aim of this project is to identify, via a functional high-throughput screening (HTS) approach, small molecule positive allosteric modulators (PAMs) and/or allosteric agonists of the M1 muscarinic acetylcholine receptor (mAChR) that are cell permeable, possess submicromolar potency, and show greater than 10-fold selectivity over the other mAChRs (M2-M5). The identified small molecular probe ML137 (CID-44251556) can be used for in vitro molecular pharmacology and electrophysiology experiments to study the receptor trafficking profile and role of selective M1 receptor activation by this unique M1 PAM chemotype. Probes developed from these efforts will greatly advance the current state of the art by aiding in the understanding of M1's role in cell-based physiology, and may extend the clinical understanding of psychotic and cognitive symptoms associated with neurodegenerative disorders, such as Alzheimer's Disease and schizophrenia.