{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:00Z","timestamp":1792172460815,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["073377\/Z\/03\/Z"],"award-info":[{"award-number":["073377\/Z\/03\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>\u03b2\u2010agonists have been used in asthma for 120\u2009years. There are two recent changes: ultra\u2010long\u2010acting agonists for COPD and new asthma guidelines recommending formoterol\/ICS inhalers phasing out short\u2010acting salbutamol inhalers. Few studies directly compare the molecular pharmacological properties of short (salbutamol, terbutaline, fenoterol), long (formoterol, salmeterol), and ultra\u2010long\u2010acting (indacaterol, olodaterol, vilanterol) \u03b2<jats:sub>2<\/jats:sub>\u2010agonists. Here, the in\u00a0vitro molecular pharmacological properties of affinity, selectivity, intrinsic efficacy, and duration of \u03b2<jats:sub>2<\/jats:sub>\u2010agonists at human \u03b2<jats:sub>2<\/jats:sub> and \u03b2<jats:sub>1<\/jats:sub>\u2010adrenoceptors and the 4 \u03b2<jats:sub>2<\/jats:sub>\u2010polymorphisms stably expressed in CHO cells were directly compared using radioligand binding and functional studies. Whilst short\u2010acting drugs were similar, there was huge variation and complete overlap in the molecular pharmacological properties of drugs labeled as long and ultra\u2010long\u2010acting \u03b2<jats:sub>2<\/jats:sub>\u2010agonists. Salmeterol and vilanterol were highly \u03b2<jats:sub>2<\/jats:sub>\u2010selective (&gt;\u20091000\u2010fold) whereas indacaterol was similar to salbutamol (40\u2010fold). Formoterol and indacaterol were the most efficacious, whereas salmeterol had the longest duration of binding. Salmeterol and vilanterol utilize a \u03b2<jats:sub>2<\/jats:sub>\u2010specific exosite (\u03b2<jats:sub>2<\/jats:sub>\u2010H296\u2010K305) for high affinity and selectivity (that does not affect intrinsic efficacy or duration) whilst the \u03b2<jats:sub>2<\/jats:sub>\u2010selectivity of formoterol and olodaterol resides elsewhere. Duration of binding closely correlated with lipophilicity. \u03b2<jats:sub>2<\/jats:sub>\u2010polymorphisms had no substantial effect on \u03b2<jats:sub>2<\/jats:sub>\u2010agonist properties. Comparison with other \u03b2\u2010ligands suggests that affinity and duration could both be improved further. However, given the very wide range of molecular pharmacological properties of \u03b2\u2010agonists that are clinically effective and widely used, non\u2010pharmacological properties (physiochemical, patient factors, devices and combination inhaler availability) may be as important in final clinical patient outcomes as the molecular pharmacological properties of the individual \u03b2<jats:sub>2<\/jats:sub>\u2010agonists themselves.<\/jats:p>","DOI":"10.1002\/prp2.70154","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T06:30:51Z","timestamp":1756708251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Comparison of the Molecular Pharmacological Properties of Current Short, Long, and Ultra\u2010Long\u2010Acting \u03b2<sub>2<\/sub>\u2010Agonists Used for Asthma and <scp>COPD<\/scp>"],"prefix":"10.1002","volume":"13","author":[{"given":"Richard G. 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