{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:22:10Z","timestamp":1779286930468,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,26]],"date-time":"2019-05-26T00:00:00Z","timestamp":1558828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Astellas Pharma Europe B.V."}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the effect of ASP2205, a selective serotonin 5\u2010HT<jats:sub>2c<\/jats:sub> receptor agonist, and Duloxetine on the urethral pressure in healthy female subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy females aged 18 to 55 years were recruited for this phase 1, single site, placebo\u2010controlled, randomized, four\u2010period, cross\u2010over study. The interventions were single oral doses of 10 and 60\u2009mg ASP2205, 80\u2009mg duloxetine, and placebo. As a pharmacodynamics endpoint, opening urethral pressure (OUP), corrected for placebo, was measured using urethral pressure reflectometry under both resting and squeezing condition of the pelvic floor at predose and 3, 6, 12, and 24\u2009hours after dosing. Safety and tolerability of ASP2205 were also compared with duloxetine and placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen healthy women signed informed consent, however, one dropped out before dosing and one dropped out after the first period, therefore, 16 subjects completed the study. Duloxetine significantly increased the OUP during both resting and squeezing condition (maximal increase 18.1 and 16.8\u2009cmH<jats:sub>2<\/jats:sub>O, respectively). Both doses of ASP2205 did not increase OUP at any time point. During squeezing OUP decreased significantly in the ASP2205 60\u2009mg group from 6 to 24\u2009hours after dosing. All subjects experienced predominantly central nervous system\u2010related side effects (eg, dizziness and nausea) during ASP2205 treatment, which was most pronounced at 60\u2009mg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ASP2205, a serotonin 5\u2010HT<jats:sub>2c<\/jats:sub> receptor agonist, does not increase the urethral pressure and it is therefore unlikely that 5\u2010HT\n<jats:sub>2c<\/jats:sub> receptor agonists can be used as a treatment for stress urinary incontinence. ASP2205 was less well tolerated than the high dose of duloxetine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24045","type":"journal-article","created":{"date-parts":[[2019,5,26]],"date-time":"2019-05-26T07:03:42Z","timestamp":1558854222000},"page":"1700-1706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of a 5\u2010HT<sub>2c<\/sub> receptor agonist on urethral closure mechanism in healthy women"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-3135","authenticated-orcid":false,"given":"Niels","family":"Klarskov","sequence":"first","affiliation":[{"name":"Department of Gynecology &amp; Obstetrics Herlev Hospital Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Van Till","sequence":"additional","affiliation":[{"name":"Medical Sciences Astellas Pharma Europe BV Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Will","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Medical Sciences Astellas Pharma Europe BV Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Cernus","sequence":"additional","affiliation":[{"name":"Medical Sciences Astellas Pharma Europe BV Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Will","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Medical Sciences Astellas Pharma Europe BV Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,26]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20798"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(87)90314-1"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(88)90400-1"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.01.114"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23282"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.08.041"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00746-8"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21344"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00297.2009"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00614.2017"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2019.02.004"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-013-2269-6"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2007.06922.x"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2003.28"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-016-2964-1"},{"issue":"3","key":"e_1_2_7_1_17_1","first-page":"B4412","article-title":"Urethral pressure reflectometry. 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