{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:53:47Z","timestamp":1789610027702,"version":"build-2803163510"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.ejphar.2021.173995","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T16:59:37Z","timestamp":1614790777000},"page":"173995","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Efficacy of the combination of KPR-5714, a novel transient receptor potential melastatin 8 (TRPM8) antagonist, and \u03b23-adrenoceptor agonist or anticholinergic agent on bladder dysfunction in rats with bladder overactivity"],"prefix":"10.1016","volume":"899","author":[{"given":"Naoki","family":"Aizawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takemitsu","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Goi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoe","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.173995_bib1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/nau.10052","article-title":"The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society","volume":"21","author":"Abrams","year":"2002","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib2","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s00345-016-1908-1","volume":"35","author":"Abrams","year":"2017","journal-title":"World J. Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib3","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1002\/nau.23532","article-title":"KPR-2579, a novel TRPM8 antagonist, inhibits acetic acid-induced bladder afferent hyperactivity in rats","volume":"37","author":"Aizawa","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib4","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.eururo.2012.08.056","article-title":"Effects of mirabegron, a novel beta3-adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin","volume":"62","author":"Aizawa","year":"2012","journal-title":"Eur. Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib5","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/nau.22571","article-title":"Effects of L-arginine, mirabegron, and oxybutynin on the primary bladder afferent nerve activities synchronized with reflexic, rhythmic bladder contractions in the rat","volume":"34","author":"Aizawa","year":"2015","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib6","doi-asserted-by":"crossref","first-page":"7646","DOI":"10.1038\/s41598-017-07898-y","article-title":"Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction","volume":"7","author":"Aizawa","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2021.173995_bib7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/nau.20940","article-title":"Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivity","volume":"30","author":"Aizawa","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib8","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.juro.2014.09.005","article-title":"Selective inhibitory effect of imidafenacin and 5-hydroxymethyl tolterodine on capsaicin sensitive C fibers of the primary bladder mechanosensitive afferent nerves in the rat","volume":"193","author":"Aizawa","year":"2015","journal-title":"J. Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.lfs.2018.12.031","article-title":"RQ-00434739, a novel TRPM8 antagonist, inhibits prostaglandin E2-induced hyperactivity of the primary bladder afferent nerves in rats","volume":"218","author":"Aizawa","year":"2019","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2021.173995_bib10","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/nau.22920","article-title":"Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats","volume":"36","author":"Aizawa","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib11","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/nau.21212","article-title":"Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat","volume":"31","author":"Aizawa","year":"2012","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib12","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0031-6997(25)00442-9","article-title":"Pharmacology of lower urinary tract smooth muscles and penile erectile tissues","volume":"45","author":"Anderson","year":"1993","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ejphar.2021.173995_bib13","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1073\/pnas.231243698","article-title":"Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells","volume":"98","author":"Birder","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejphar.2021.173995_bib14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.urology.2004.08.063","article-title":"The urothelium in overactive bladder: passive bystander or active participant?","volume":"64","author":"de Groat","year":"2004","journal-title":"Urology"},{"key":"10.1016\/j.ejphar.2021.173995_bib15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1124\/jpet.116.237313","article-title":"Pharmacological characterization of a novel beta 3 adrenergic agonist, vibegron: evaluation of antimuscarinic receptor selectivity for combination therapy for overactive bladder","volume":"360","author":"Di Salvo","year":"2017","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.173995_bib16","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/nau.22609","article-title":"Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013","volume":"33","author":"Drake","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.autneu.2011.05.006","article-title":"Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats","volume":"164","author":"Hayashi","year":"2011","journal-title":"Auton. Neurosci."},{"key":"10.1016\/j.ejphar.2021.173995_bib18","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/nau.20497","article-title":"Cold environmental stress induces detrusor overactivity via resiniferatoxin-sensitive nerves in conscious rats","volume":"27","author":"Imamura","year":"2008","journal-title":"Neurourol. Urodyn."},{"key":"10.1016\/j.ejphar.2021.173995_bib19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/luts.12050","article-title":"Pathways involving beta-3 adrenergic receptors modulate cold stress-induced detrusor overactivity in conscious rats","volume":"7","author":"Imamura","year":"2015","journal-title":"Low. Urin. Tract. Symptoms"},{"key":"10.1016\/j.ejphar.2021.173995_bib20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/bju.13225","article-title":"Functional role of the transient receptor potential melastatin 8 (TRPM8) ion channel in the urinary bladder assessed by conscious cystometry and ex vivo measurements of single-unit mechanosensitive bladder afferent activities in the rat","volume":"117","author":"Ito","year":"2016","journal-title":"BJU Int."},{"key":"10.1016\/j.ejphar.2021.173995_bib21","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/S0022-5347(05)64634-4","article-title":"Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats","volume":"168","author":"Kaidoh","year":"2002","journal-title":"J. Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib22","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.eururo.2018.03.020","article-title":"Efficacy and tolerability of mirabegron compared with antimuscarinic monotherapy or combination therapies for overactive bladder: a systematic review and network meta-analysis","volume":"74","author":"Kelleher","year":"2018","journal-title":"Eur. Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib23","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bmc.2016.11.049","article-title":"Synthesis and optimization of novel alpha-phenylglycinamides as selective TRPM8 antagonists","volume":"25","author":"Kobayashi","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejphar.2021.173995_bib24","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/cne.20794","article-title":"Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta\/c-fibers and colocalization with trk receptors","volume":"493","author":"Kobayashi","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.ejphar.2021.173995_bib25","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00210-012-0755-x","article-title":"Bladder selectivity of the novel beta(3)-agonist ritobegron (KUC-7483) explored by in vitro and in vivo studies in the rat","volume":"385","author":"Maruyama","year":"2012","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.173995_bib26","doi-asserted-by":"crossref","first-page":"173096","DOI":"10.1016\/j.ejphar.2020.173096","article-title":"Effects of vibegron, a novel beta3-adrenoceptor agonist, and its combination with imidafenacin or silodosin in a rat with partial bladder outlet obstruction","volume":"878","author":"Maruyama","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.173995_bib27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature719","article-title":"Identification of a cold receptor reveals a general role for TRP channels in thermosensation","volume":"416","author":"McKemy","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2021.173995_bib28","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/jpet.115.228684","article-title":"DFL23448, A novel transient receptor potential melastin 8-selective ion channel antagonist, modifies bladder function and reduces bladder overactivity in awake rats","volume":"356","author":"Mistretta","year":"2016","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.173995_bib29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1471-2490-6-31","article-title":"Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders","volume":"6","author":"Mukerji","year":"2006","journal-title":"BMC Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2490-6-6","article-title":"Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations","volume":"6","author":"Mukerji","year":"2006","journal-title":"BMC Urol."},{"key":"10.1016\/j.ejphar.2021.173995_bib31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1124\/jpet.119.263616","article-title":"KPR-5714, a novel transient receptor potential melastatin 8 antagonist, improves overactive bladder via inhibition of bladder afferent hyperactivity in rats","volume":"373","author":"Nakanishi","year":"2020","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.173995_bib32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0092-8674(02)00652-9","article-title":"A TRP channel that senses cold stimuli and menthol","volume":"108","author":"Peier","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2021.173995_bib33","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1124\/jpet.106.115840","article-title":"Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function","volume":"321","author":"Takasu","year":"2007","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.173995_bib34","doi-asserted-by":"crossref","first-page":"172727","DOI":"10.1016\/j.ejphar.2019.172727","article-title":"Effects of the combination of vibegron and imidafenacin on bladder function in urethane-anesthetized rats","volume":"864","author":"Yamazaki","year":"2019","journal-title":"Eur. J. Pharmacol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921001485?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921001485?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:47:50Z","timestamp":1757976470000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921001485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":34,"alternative-id":["S0014299921001485"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.173995","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy of the combination of KPR-5714, a novel transient receptor potential melastatin 8 (TRPM8) antagonist, and \u03b23-adrenoceptor agonist or anticholinergic agent on bladder dysfunction in rats with bladder overactivity","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.173995","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"173995"}}