{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:02:00Z","timestamp":1787770920223,"version":"build-2784847793"},"reference-count":66,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"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":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide\u2013dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for \u03b2<jats:sub>3<\/jats:sub> agonists, including the bladder wall vasculature and <jats:italic>muscularis mucosa<\/jats:italic>. (c) Several TRP channels (TRPV<jats:sub>1<\/jats:sub>, TRPV<jats:sub>4<\/jats:sub>, TRPA<jats:sub>1<\/jats:sub>, and TRPM<jats:sub>4<\/jats:sub>) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF\u2010\u03b2 pathway\u2014the canonical fibrosis pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above\u00a0mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24228","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T13:15:25Z","timestamp":1574082925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["New targets for overactive bladder\u2014ICI\u2010RS 2109"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-5983","authenticated-orcid":false,"given":"Christopher Henry","family":"Fry","sequence":"first","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7320-4931","authenticated-orcid":false,"given":"Basu","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Hashitani","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Nagoya City University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-3486","authenticated-orcid":false,"given":"Karl\u2010Erik","family":"Andersson","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine Lund University Lund Sweden"},{"name":"Institute for Regenerative Medicine Wake Forest University School of Medicine Winston\u2010Salem North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-9013","authenticated-orcid":false,"given":"Karen","family":"McCloskey","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences Queens University Belfast Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita\u00a0I.","family":"Jabr","sequence":"additional","affiliation":[{"name":"Division of Biochemical Sciences, Faculty of Health and Biomedical Sciences University of Surrey Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J.","family":"Drake","sequence":"additional","affiliation":[{"name":"Bristol Medical School University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.02.038"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12262"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12247"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00488.2018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-016-1255-1"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2012.11421.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22665"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.09.020"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.10.055"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00748.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14669"},{"key":"e_1_2_9_14_1","first-page":"1367","article-title":"Evidence for beta3\u2010adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods","volume":"288","author":"Takeda M","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005392-200101000-00071"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.01.007"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000052314"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14349.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.074"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00392.2016"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23224"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2005.05455.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511550"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00166.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.01.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-019-03088-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.04.082"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655999750042114"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2014.01.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP275845"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12577"},{"key":"e_1_2_9_32_1","first-page":"67","article-title":"TRP channels as lower urinary tract sensory targets","volume":"7","author":"Andersson KE","year":"2019","journal-title":"Med Sci"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005333107"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00008.2014"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2490-6-6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.216010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11040117"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00270.2015"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-018-1542-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2011.194"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2006.03.039"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00495.2010"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09935.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405621200"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00389"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.5.R1699"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2009.102"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00142.2014"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00363.2012"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23725"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-5895-1_5"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12009"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274492"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2018.12.004"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00114"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/124624"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13684"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.23721"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00042.2014"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13529"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00602.2015"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.12.014"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61255-1"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4173"},{"key":"e_1_2_9_65_1","unstructured":"Moldwin R Kitt M Mangel J et al. A phase 2 study in women with interstitial cystitis\/bladder pain syndrome (IC\/BPS) of the novel P2X3 antagonist AF\u2010219. Paper presented at: International Continence society meeting 2015 abstr 23."},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.225268"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-016-1312-9"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnau.24228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.24228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/nau.24228","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.24228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:23:20Z","timestamp":1692951800000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.24228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,18]]},"references-count":66,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/nau.24228"],"URL":"https:\/\/doi.org\/10.1002\/nau.24228","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"value":"0733-2467","type":"print"},{"value":"1520-6777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,18]]},"assertion":[{"value":"2019-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}