AF-DX 116 (Otenzepad), M2 antagonist

Supplementary info

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

Activity summary

Muscarinic Acetylcholine Receptor 2 (M2) also known as CHRM2 is a G protein-coupled receptor (GPCR) with a molecular mass of about 66 kDa. This receptor is predominantly expressed in cardiac tissue particularly in the atria and plays a fundamental role in the parasympathetic nervous system by mediating the effects of acetylcholine. M2 receptors participate in negative feedback control by inhibiting adenylate cyclase which reduces the conversion of ATP to cAMP affecting heart rate and contractility. These receptors are an important target for anti-muscarinic agents like otenzepad and AF-DX 116 which inhibit the receptor's activity.

Biological function summary

Muscarinic acetylcholine receptors perform diverse functions participating in the regulation of autonomic nervous system responses. M2 receptors are not part of a large protein complex but function closely with other GPCRs to maintain homeostasis. They modulate the activity of various ion channels contributing to their role in cardiac physiological processes. Anti-muscarinic antibodies can specifically target M2 for therapeutic interventions which further helps in dissecting their biological functionality.

Pathways

M2 receptors play essential roles in both the autonomic nervous system and the cardiovascular system. They are involved in the cholinergic signaling pathway which modulates heart rate by influencing ion channel activity and reducing intracellular cAMP levels. Their interaction with proteins like G-proteins and ion channels such as Kir3.1 underlines their importance in these pathways. M2 muscarinic receptors are closely linked with other muscarinic receptors showing a collaborative action in signaling cascades.

Associated diseases and disorders

M2 receptors have connections with cardiovascular diseases and certain neurological disorders. Alterations in M2 receptor function or expression can lead to conditions like bradycardia where the heart rate is abnormally slow and are also implicated in cognitive disorders linked to cholinergic dysfunction. The receptor's interaction with other muscarinic receptors like M1 and M4 further ties it to these pathologies amplifying its relevance in understanding complex diseases. Anti-muscarinic antibodies targeting M2 can modulate these interactions offering potential therapeutic benefits.