{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:28:54Z","timestamp":1790162934918,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T00:00:00Z","timestamp":1499385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Prince Charles Hospital Foundation","award":["ER0215-22"],"award-info":[{"award-number":["ER0215-22"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Mirabegron has been classified as a \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of \u03b2\u2010adrenoceptor subtype antagonists. In view of its phenylethanolamine structure, we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Right atrial trabeculae, from non\u2010failing hearts, were paced and contractile force measured at 37\u00b0C. Single concentrations of mirabegron were added in the absence or presence of the phosphodiesterase inhibitor 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX), \u03b2<jats:sub>3<\/jats:sub>(L\u2010748,337), \u03b2<jats:sub>1<\/jats:sub>(CGP 20712A), \u03b2<jats:sub>2<\/jats:sub>(ICI 118,551) \u2010adrenoceptor antagonists, neuronal uptake inhibitors desipramine or phenoxybenzamine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Mirabegron significantly increased contractile force in human right atrium (1\u00a0\u03bcM, 7.6\u00a0\u00b1\u00a02.6%,<jats:italic>n<\/jats:italic>\u00a0=\u00a07; 10\u00a0\u03bcM, 10.2\u00a0\u00b1\u00a01.5%,<jats:italic>n<\/jats:italic>\u00a0=\u00a022 compared with (\u2212)\u2010isoprenaline<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). In the presence of IBMX, mirabegron (10\u00a0\u03bcM) caused a greater contraction. L\u2010748,337 (100\u00a0nM) had no effect on the increase in contractile force caused by mirabegron (10\u00a0\u03bcM). In contrast, mirabegron (10\u00a0\u03bcM) reduced contractile force in the presence of CGP 20712A, which was not affected by L\u2010748,337 (100\u00a0nM) or ICI 118,551 (50\u00a0nM). Mirabegron (10\u00a0\u03bcM) also reduced contractile force in the presence of desipramine or phenoxybenzamine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Mirabegron increases human atrial force through \u03b2<jats:sub>1<\/jats:sub>\u2010 but not \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptors. Desipramine and phenoxybenzamine block neuronal uptake and conceivably prevent mirabegron from releasing noradrenaline. A non\u2010specific cardiodepressant effect is not mediated through \u03b2<jats:sub>3<\/jats:sub>(or \u03b2<jats:sub>2<\/jats:sub>)\u2010adrenoceptors, consistent with lack of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor function on human atrial contractility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13897","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T15:18:47Z","timestamp":1496416727000},"page":"2706-2715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["The \u03b2<sub>3<\/sub>\u2010adrenoceptor agonist mirabegron increases human atrial force through \u03b2<sub>1<\/sub>\u2010adrenoceptors: an indirect mechanism?"],"prefix":"10.1111","volume":"174","author":[{"given":"Weilan","family":"Mo","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences Queensland University of Technology Brisbane Qld Australia"},{"name":"Northside Clinical School of Medicine 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