{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T08:48:58Z","timestamp":1760345338222,"version":"3.37.3"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Transient receptor potential melastatin 8 (TRPM8) has a role in the abnormal sensory transduction of the bladder and is involved in the pathophysiology of hyperactivity bladder disorders. The aim of this study is to examine the effects of KPR\u20105714, a novel and selective TRPM8 antagonist, on voiding dysfunction induced by bladder afferent hyperactivity via mechanosensitive C\u2010fibers in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of intragastric administration of KPR\u20105714 on bladder overactivity induced by intravesical instillation of 10\u2009mM ATP were investigated using cystometry in conscious female rats. We examined the effects of oral administration of KPR\u20105714 on voiding behavior using a metabolic cage in normal male rats and rats with an intratesticular injection of 3% acetic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In cystometry measurements, the intercontraction interval was decreased by intravesical ATP instillation. KPR\u20105714 (0.1, 0.3, and 1\u2009mg\/kg) dose\u2010dependently prolonged the shortened intercontraction interval provoked by ATP. In voiding behavior measurements, intratesticular injection of acetic acid decreased the mean voided volume and increased voiding frequency. KPR\u20105714 (0.1 and 0.3\u2009mg\/kg) dose\u2010dependently increased the mean voided volume and decreased voiding frequency without affecting the total voided volume in these rats. However, KPR\u20105714 (1 and 10\u2009mg\/kg) did not influence the voiding behavior in normal rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present results suggest that KPR\u20105714 improves voiding dysfunction by inhibiting the enhanced activity of mechanosensitive bladder C\u2010fibers in rats with bladder overactivity and shows no significant change in voiding behavior in normal rats.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24951","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T19:03:22Z","timestamp":1652209402000},"page":"1336-1343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["KPR\u20105714, a selective transient receptor potential melastatin 8 antagonist, improves voiding dysfunction in rats with bladder overactivity but does not affect voiding behavior in normal rats"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-6132","authenticated-orcid":false,"given":"Shinjiro","family":"Watanabe","sequence":"first","affiliation":[{"name":"Drug Discovery Research Laboratory, Kissei Pharmaceutical Co., Ltd.  Azumino Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikazu","family":"Fujimori","sequence":"additional","affiliation":[{"name":"Drug Discovery Research Laboratory, Kissei Pharmaceutical Co., Ltd.  Azumino Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akane","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratory, Kissei Pharmaceutical Co., Ltd.  Azumino Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun\u2010ichi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Drug Discovery Research Laboratory, Kissei Pharmaceutical Co., Ltd.  Azumino Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Hirasawa","sequence":"additional","affiliation":[{"name":"Chemistry Research Laboratory, Kissei Pharmaceutical Co., Ltd.  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