{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T10:16:01Z","timestamp":1768644961131,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T00:00:00Z","timestamp":1455753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22591802"],"award-info":[{"award-number":["22591802"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K10633"],"award-info":[{"award-number":["15K10633"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the efficacy of combination therapy of a selective \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor agonist (mirabegron) and muscarinic acetylcholine receptor antagonists (a selective muscarinic acetylcholine receptor<jats:sub>2<\/jats:sub> antagonist: methoctramine hemihydrate or a selective muscarinic acetylcholine receptor<jats:sub>3<\/jats:sub> antagonist; 4\u2010DAMP) compared with monotherapy of either agent in rats with oxotremorine methiodide (a non\u2010selective muscarinic acetylcholine receptor agonist)\u2010induced bladder overactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cystometry was carried out in conscious female rats with intravesical instillation of oxotremorine methiodide (200\u00a0\u03bcmol\/L). Either mirabegron (0.3\u20133\u00a0mg\/kg), methoctramine (0.1\u20131\u00a0mg\/kg) or 4\u2010DAMP (0.03\u20130.3\u00a0mg\/kg) was cumulatively applied intravenously. Also, the effects of combined application of mirabegron (3\u00a0mg\/kg) plus methoctramine (1\u00a0mg\/kg) or 4\u2010DAMP (0.3\u00a0mg\/kg) on cystometric parameters were compared with those of single\u2010agent monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intravesical instillation of oxotremorine methiodide induced bladder overactivity, as evidenced by decreases in threshold pressure and bladder capacity. In oxotremorine methiodide\u2010treated rats, single application of mirabegron (1, 3\u00a0mg\/kg), methoctramine (0.3, 1\u00a0mg\/kg) or 4\u2010DAMP (0.1, 0.3\u00a0mg\/kg) decreased baseline pressure and increased bladder capacity. In addition, reductions in threshold pressure and maximal voiding pressure were also seen after the administration of 4\u2010DAMP (0.3\u00a0mg\/kg). The combined treatment of mirabegron plus 4\u2010DAMP induced a larger increase in bladder capacity compared with monotherapy of either drug, whereas there were no significant changes in cystometric parameters between the combination therapy of mirabegron plus methoctramine and monotherapy of either drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the combination therapy of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor agonists plus muscarinic acetylcholine receptor<jats:sub>3<\/jats:sub> antagonists is more effective compared with monotherapy for the treatment of bladder overactivity. In contrast, the efficacy of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor agonists might not be increased by the addition of muscarinic acetylcholine receptor<jats:sub>2<\/jats:sub> antagonists.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.13066","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T21:57:19Z","timestamp":1455832639000},"page":"425-430","source":"Crossref","is-referenced-by-count":15,"title":["Combination therapy with \u03b2<sub>3<\/sub>\u2010adrenoceptor agonists and muscarinic acetylcholine receptor antagonists: Efficacy in rats with bladder overactivity"],"prefix":"10.1111","volume":"23","author":[{"given":"Akira","family":"Furuta","sequence":"first","affiliation":[{"name":"Department of Urology Jikei University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Urology Tokyo Metropolitan Rehabilitation Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Urology Jikei University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Urology Jikei University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Egawa","sequence":"additional","affiliation":[{"name":"Department of Urology Jikei University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania 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