Abediterol (LAS100977), an inhaled long-acting β 2 -adrenoceptor agonist, has a fast association rate and long residence time at receptor

Abstract This study describes the association rate and residence time of abediterol, a novel long-acting β 2 -adrenoceptor agonist (LABA) in Phase II development for treatment of asthma and COPD, in comparison with indacaterol, olodaterol, vilanterol and salmeterol, for both human β 1 - and β 2 -adrenoceptors. Abediterol association and dissociation rates were monitored directly by using its tritiated form. Moreover, association was determined indirectly using experimental K i and k off obtained from assays performed with unlabelled compound. Dissociation was also studied indirectly by measuring the association rate of 3 H-CGP12177 to beta adrenoceptors previously occupied by unlabelled compounds. Abediterol shows a fast association for the β 2 -adrenoceptor (k on 1.4 × 10 7 ± 1.8 × 10 6  M −1  min −1 ) while its dissociation rate is between 30 and 64 times slower than that of the reference LABA compounds tested, with a residence time of 91.3 ± 13.3 min (measured directly) and 185.5 ± 7.5 min (measured indirectly). Abediterol shows kinetic selectivity for the β 2 - over the β 1 -adrenoceptor, with a dissociation rate from the β 1 -adrenoceptor similar to the other LABA compounds tested. In conclusion, abediterol is a potent LABA with a fast association rate and a long residence time at β 2 -adrenoceptors. These data are in agreement with the onset and duration of action of abediterol shown in humans.