Batefenterol (TD-5959) (GSK961081, TD-5959) is a muscarinic receptor antagonist and β2-adrenoceptor agonist. It displays high affinity for hM2, hM3 muscarinic and hβ2-adrenoceptor (Ki:1.4/1.3/3.7 nM).

β2-adrenoceptor:3.7 nM (Ki, cell free), M2 (human):1.4 nM (Ki, cell free), M3 (human):1.3 nM (Ki, cell free)

In competition radioligand binding studies at human recombinant receptors, Batefenterol displays high affinity for hM2 (Ki; 1.4 nM), hM3 muscarinic receptors (Ki: 1.3 nM) and hβ2-adrenoceptors (Ki: 3.7 nM). Batefenterol behaves as a potent hβ2-adrenoceptor agonist (EC50: 0.29 nM for stimulation of cAMP levels) with 440- and 320-fold functional selectivity over hβ1- and hβ3-adrenoceptors, respectively [1].

In the guinea pig broncho-protection assay, inhaled Batefenterol produces potent, dose-dependent inhibition of bronchoconstrictor responses via MA (ED50: 33.9 μg/mL), BA (ED50: 14.1 μg/mL), and MABA (ED50: 6.4 μg/mL) mechanisms. Significant bronchoprotective effects of Batefenterol are evident in guinea pigs via MA, BA, and MABA mechanisms for up to 7 days after dosing[1]. In guinea pig isolated trachea expressing native muscarinic M3 and β2, Batefenterol produces smooth muscle relaxation through a dual mechanism involving competitive antagonism of the M3 receptor (EC50: 50 nM) and agonism of the β2 receptor (EC50: 25 nM). The combined effect on both muscarinic receptors and β2 receptors is more potent than either function working alone (EC50: 10 nM) [2].