VU0152100, M4 positive allosteric modulator

Supplementary info

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

Activity summary

The Muscarinic Acetylcholine Receptor M4 also known as M4 receptor or CHRM4 is a G protein-coupled receptor with a mass of about 60-70 kDa. It is part of the muscarinic receptor family which includes five subtypes. Expression of CHRM4 occurs broadly in the central nervous system particularly within the brain's striatum and cortex regions influencing neuronal activity. The M4 muscarinic receptor plays a critical role in modulating neurotransmission responding to the neurotransmitter acetylcholine.

Biological function summary

The M4 muscarinic receptor influences several important processes by coupling with G proteins primarily inhibiting adenylate cyclase activity which results in reduced cyclic AMP levels. The M4 receptor is not generally part of a larger protein complex; rather it functions through interaction with associated proteins like Gi/Go proteins. This negative regulation can lead to various downstream effects that impact neural signaling making M4 receptors important in synaptic plasticity cognition and motor control.

Pathways

M4 muscarinic receptors participate significantly in the dopaminergic and cholinergic signaling pathways. M4 receptors interact closely with dopamine D1 receptors affecting dopamine release in the brain. This integration into these pathways highlights M4's role in motor and reward circuits showing its involvement alongside proteins such as other muscarinic receptors and dopamine-related proteins. These pathway involvements make it a target for pharmacological research in neurological contexts.

Associated diseases and disorders

Alterations in M4 receptor function have connections to schizophrenia and Parkinson's disease. In schizophrenia imbalances of muscarinic receptors including M4 relate to cognitive deficits and are a focus for therapeutic strategies. Meanwhile in Parkinson's disease M4 receptors have been associated with motor control issues due to their role in modulating dopaminergic activity. Additionally studies point to the involvement of other muscarinic receptors and dopaminergic proteins in these disorders making M4 an important player in understanding and potentially treating these conditions.