VU0119498, M1 muscarinic receptor agonist and pan mAChR M3, M5 PAM

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

Muscarinic acetylcholine receptors also known as mAChRs are a group of G protein-coupled receptors that bind acetylcholine. They include five distinct subtypes: CHRM1 CHRM2 CHRM3 CHRM4 and CHRM5. These receptors have variable molecular masses ranging from approximately 50 to 60 kDa. Expression of muscarinic receptors is widespread present in both central and peripheral nervous systems and in non-neuronal tissues such as heart and smooth muscle. Each subtype has a unique pattern of distribution affecting how the body reacts to stimuli.

Biological function summary

Muscarinic receptors mediate parasympathetic nervous system responses. They do not function in isolation and may form complexes with other membrane proteins. mAChRs play roles in reducing heart rate constricting bronchi increasing secretions and modulating neurochemical activities in the central nervous system. Arecaidine can act as a muscarinic agonist whereas aclidinium serves as a muscarinic antagonist both influencing receptor activity through different pathways.

Pathways

Muscarinic receptors participate in the PI3K/AKT and MAPK signaling pathways. These pathways are key for cellular responses to environmental changes. For example muscarinic receptors in the cardiac tissue influence heart rate through these pathways interacting with proteins like Gi/o proteins. mAChRs also activate pathways involving other G protein receptors like adrenergic receptors to regulate vascular resistance and secretory processes.

Associated diseases and disorders

Muscarinic receptors are linked to Alzheimer’s disease and chronic obstructive pulmonary disease (COPD). In Alzheimer’s imbalances in muscarinic receptor signaling can disrupt cognitive function. The CHRM1 subtype is particularly implicated in neurotransmission abnormalities associated with this disease. In COPD the CHRM3 subtype’s regulation of bronchoconstriction becomes clinically relevant. Therapeutic targeting of these receptors using antagonists like aclidinium helps manage symptoms and improve patient outcome.