RT Journal Article
SR Electronic
T1 In Vitro Pharmacological Characterization of Vilanterol, a Novel Long-Acting β2-Adrenoceptor Agonist with 24-Hour Duration of Action
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 218
OP 230
DO 10.1124/jpet.112.198481
VO 344
IS 1
A1 Slack, Robert J.
A1 Barrett, Victoria J.
A1 Morrison, Valerie S.
A1 Sturton, Richard G.
A1 Emmons, Amanda J.
A1 Ford, Alison J.
A1 Knowles, Richard G.
YR 2013
UL http://jpet.aspetjournals.org/content/344/1/218.abstract
AB Vilanterol trifenatate (vilanterol) is a novel, long-acting β2-adrenoceptor (β2-AR) agonist with 24 h activity. In this study, we describe the preclinical pharmacological profile of vilanterol using radioligand binding and cAMP studies in recombinant assays as well as human and guinea pig tissue systems to characterize β2-AR binding and functional properties. Vilanterol displayed a subnanomolar 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 after 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 chronic obstructive pulmonary disease (COPD).