Abstract

Vilanterol trifenatate (vilanterol) is a novel long acting β₂–adrenoceptor (β₂-AR) agonist with 24 hour activity. In this study we describe the pre-clinical pharmacological profile of vilanterol using radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP) studies in recombinant assays as well as human and guinea pig tissue systems to characterise β₂-AR binding and functional properties. Vilanterol displayed a sub-nanomolar affinity for the β₂-AR that was comparable with that of salmeterol but higher than olodaterol, formoterol and indacaterol. In cAMP functional activity studies vilanterol demonstrated similar selectivity as salmeterol for β₂- over β₁-AR and β₃-AR, but a significantly improved selectivity profile than formoterol and indacaterol. Vilanterol also showed a level of intrinsic efficacy that was comparable to indacaterol but significantly greater than that of salmeterol. In cellular cAMP production and tissue based studies measuring persistence and reassertion, vilanterol had a persistence of action comparable with indacaterol and longer than formoterol. In addition, vilanterol demonstrated reassertion activity in both cell and tissue systems that was comparable with salmeterol and indacaterol but longer than formoterol. In human airways vilanterol was shown to have a faster onset and longer duration of action than salmeterol, exhibiting a significant level of bronchodilation 22 h post-treatment. From these investigations the data for vilanterol are consistent, showing that it is a novel, potent and selective β₂-AR receptor agonist with a long duration of action. This pharmacological profile combined with clinical data is consistent with once a day dosing of vilanterol in the treatment of both asthma and COPD.