Muscarinic acetylcholine receptor M3 and Beta-2 adrenergic receptor (M3R/ADRB2)

GSK961081, also known as Batefenterol, is a bifunctional molecule belonging to the Muscarinic Antagonist-Beta2 Agonist (MABA) class (PMID: 24655453). It simultaneously targets the Muscarinic Acetylcholine Receptor M3 and the Beta-2 Adrenergic Receptor, both of which are G protein-coupled receptors located on airway smooth muscle cells (PubChem CID: 25141144). The antagonism of M3 receptors inhibits the bronchoconstrictive effects of acetylcholine, while the agonism of Beta-2 receptors stimulates bronchodilation through increased cAMP production (PMID: 22491779). This dual action is intended to provide enhanced therapeutic benefit for patients with Chronic Obstructive Pulmonary Disease (COPD) and asthma. Systemic pharmacokinetics are a critical aspect of its development, as the drug is designed for local action in the lungs with minimal systemic absorption to avoid off-target cardiovascular and glandular side effects (ClinicalTrials.gov: NCT01411111). Clinical studies often focus on the systemic pharmacokinetics of GSK961081 to ensure that its systemic levels remain below the threshold for adverse events like tachycardia. The molecule represents a significant advancement in respiratory medicine by combining two established mechanisms of action into a single chemical entity.

Other names

CHRM3ADRB2MABA targetsBatefenterol targetsMuscarinic M3 receptorBeta-2 adrenoceptor

Dual pharmacology involving antagonism of the M3 muscarinic receptor and agonism of the beta-2 adrenergic receptor.