Beta-2 adrenergic receptor and Muscarinic acetylcholine receptor M3 (ADRB2/CHRM3)

The Beta-2 adrenergic receptor (ADRB2) and the Muscarinic acetylcholine receptor M3 (CHRM3) are two distinct G protein-coupled receptors (GPCRs) that serve as primary regulators of airway smooth muscle tone [UniProt P07550, P20366]. ADRB2 is a Gs-coupled receptor that, upon activation, increases intracellular cyclic AMP levels to induce bronchodilation and counteract inflammatory responses [StatPearls]. In contrast, CHRM3 is a Gq-coupled receptor that mediates bronchoconstriction and mucus hypersecretion when stimulated by acetylcholine [StatPearls]. Dual targeting of these receptors is a highly effective therapeutic strategy for managing obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma [Pharmacology & Therapeutics]. This is achieved through the use of Muscarinic Antagonist Beta-2 Agonist (MABA) molecules or fixed-dose combinations of long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) [Journal of Medicinal Chemistry]. By simultaneously promoting relaxation pathways and inhibiting contraction pathways, these therapies offer superior clinical efficacy in improving lung function and reducing exacerbations compared to monotherapy [Pharmacology & Therapeutics]. Safety considerations for drugs hitting these targets include potential cardiovascular effects like tachycardia and antimuscarinic side effects such as dry mouth [StatPearls].

Other names

Beta-2 adrenoceptorM3 muscarinic receptorADRB2CHRM3Muscarinic acetylcholine receptor M3Beta-2 adrenergic receptorMABA target

Dual pharmacology involving the agonism of the beta-2 adrenergic receptor (increasing cAMP) and the antagonism of the M3 muscarinic receptor (inhibiting calcium-mediated contraction), resulting in synergistic airway smooth muscle relaxation [StatPearls, Pharmacology & Therapeutics].