{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:40:10Z","timestamp":1789810810575,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Revefenacin (<jats:styled-content style=\"fixed-case\">TD<\/jats:styled-content>\u20104208) is a novel, long\u2010acting, and lung\u2010selective muscarinic cholinergic receptor (<jats:styled-content style=\"fixed-case\">mAChR<\/jats:styled-content>) antagonist in development as a nebulized inhalation solution for the treatment of chronic obstructive pulmonary disease (<jats:styled-content style=\"fixed-case\">COPD<\/jats:styled-content>) patients. This study evaluated the pharmacology of revefenacin at human recombinant<jats:styled-content style=\"fixed-case\">mAChR<\/jats:styled-content>s and in airway tissues from rats, guinea pigs, and humans. At human recombinant<jats:styled-content style=\"fixed-case\">mAChR<\/jats:styled-content>s, revefenacin displayed high affinity (<jats:styled-content style=\"fixed-case\">pK<jats:sub>I<\/jats:sub><\/jats:styled-content>\u00a0=\u00a08.2\u20109.8) and behaved as a competitive antagonist (<jats:styled-content style=\"fixed-case\">pKI<\/jats:styled-content>, apparent\u00a0=\u00a09.4\u201010.9) at the five human recombinant<jats:styled-content style=\"fixed-case\">mAChR<\/jats:styled-content>s. Kinetic studies demonstrated that revefenacin dissociated significantly slower from the hM<jats:sub>3<\/jats:sub>(<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>\u00a0=\u00a082\u00a0minutes) compared to the<jats:styled-content style=\"fixed-case\">hM<\/jats:styled-content><jats:sub>2<\/jats:sub>(<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>\u00a0=\u00a06.9\u00a0minutes) mAChR at 37\u00b0C, thereby making it kinetically selective for the former subtype. Similarly, in functional studies, revefenacin\u2010mediated antagonism of acetylcholine (ACh)\u2010evoked calcium mobilization responses were reversed less rapidly at hM<jats:sub>3<\/jats:sub>compared to the hM<jats:sub>2<\/jats:sub>mAChR. In isolated tracheal tissues from rat and guinea pig and isolated bronchial tissues from humans, revefenacin potently antagonized mAChR\u2010mediated contractile responses. Furthermore, the antagonistic effects of revefenacin in rat, guinea pig, and human airway tissues were slowly reversible (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>of 13.3, &gt;16, and &gt;10\u00a0hours, respectively). These data demonstrate that revefenacin is a potent, high affinity, and selective functional mAChR antagonist with kinetic selectivity for the hM<jats:sub>3<\/jats:sub>receptor and produces potent and long\u2010lasting antagonism of mAChR\u2010mediated contractile responses in rat, guinea pig, and human airway tissue. These data suggest that revefenacin has the potential to be a potent once\u2010daily dosed inhaled bronchodilator in COPD patients.<\/jats:p>","DOI":"10.1002\/prp2.400","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T09:22:57Z","timestamp":1525080177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pharmacological properties of revefenacin (<scp>TD<\/scp>\u20104208), a novel, nebulized long\u2010acting, and lung selective muscarinic antagonist, at human recombinant muscarinic receptors and in rat, guinea pig, and human isolated airway tissues"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-2756","authenticated-orcid":false,"given":"Sharath S.","family":"Hegde","sequence":"first","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Teresa","family":"Pulido\u2010Rios","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Luttmann","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals King of Prussia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Foley","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals King of Prussia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald E.","family":"Hunsberger","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Pharmaceuticals King of Prussia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod","family":"Steinfeld","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TaeWeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Ji","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathai M.","family":"Mammen","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Jasper","sequence":"additional","affiliation":[{"name":"Theravance Biopharma U.S, Inc South San Francisco CA 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