{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:36:19Z","timestamp":1790516179559,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":60,"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":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Update on some molecular targets for new drugs to improve lower urinary tract (LUT) dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using PubMed, a search for literature on molecular targets in the LUT was performed to identify relevant clinical and animal studies. Keywords were entered as Medical Subject Headings (MeSH) or as text words. The Mesh terms were used in various combinations and usually included the terms lower urinary AND pharmacology. Other Mesh term included: bladder, urethra, CNS, physiology, afferent activity, ATP, prostanoids, cannabinoids, fibrosis. Search results were assessed for their overall relevance to this review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a normal bladder, ATP contributes little to detrusor contraction, but in a diseased bladder ATP may contribute to OAB. Selective decrease of ATP release via adenosine A1 receptor stimulation offers a potential treatment possibility. Candidates for relaxation of the smooth muscle of the urethra can be found among, for example, the receptor subtypes of PGE<jats:sub>2<\/jats:sub>, and PGD<jats:sub>2<\/jats:sub>. Drugs for relaxation of the striated sphincter can target the muscle directly or the spinal sphincter control. Fibrosis is a major problem in LUT dysfunction and agents with an inhibitory effect on the TGF\u03b2 pathway, for example relaxin and BMP7, may be promising avenues. Available drugs with a CNS site of action are often limited by low efficacy or adverse effects. Inhibitors of the glycine receptor Gly\u2010T2 or antagonists of the adenosine A2 receptor may be new alternatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>New molecular targets for drugs aiming at improvement of voiding function can be identified, but their translational impact remains to be established.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.23516","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T12:32:03Z","timestamp":1533126723000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI\u2010RS 2017"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-3486","authenticated-orcid":false,"given":"Karl\u2010Erik","family":"Andersson","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine Wake Forest University School of Medicine Winston Salem NC, and Institute of Clinical Medicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Fry","sequence":"additional","affiliation":[{"name":"Department of Uro\u2010Neurology The National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalesh","family":"Panicker","sequence":"additional","affiliation":[{"name":"Department of urology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Rademakers","sequence":"additional","affiliation":[{"name":"Department of urology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,31]]},"reference":[{"key":"e_1_2_3_2_1","unstructured":"AnderssonKE CardozoL CruzF LeeK\u2010S SuhaiA Wein AJ.Pharmacological treatment of urinary incontinence. In Incontinence. Ed by Abrams p Cardozo L Wagg A Wein A. 6th International Consultation on Incontinence Tokyo September 2016 The International Continence Society (ICS)and the International Consultation on Urological Diseases (ICUD)."},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12577"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)53509-0"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64632-0"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-013-9395-y"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)51175-1"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2680.1998.1820099.x"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-015-9478-z"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-016-1255-1"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2012.11421.x"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22487"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22455"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-014-9436-1"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8549"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11192"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2013.08.003"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.01.071"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1983.tb03397.x"},{"key":"e_1_2_3_20_1","article-title":"The unstable urethra in the female","author":"Low JA","year":"1989","journal-title":"Obstet Gynecol"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01902379"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.1016"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22815"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2012"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20511"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.04.042"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1981.tb03125.x"},{"key":"e_1_2_3_28_1","first-page":"188","article-title":"The intrinsic intramural striated sphincter of the membranous urethra","volume":"80","author":"Ho KM","year":"1997","journal-title":"Br J Urol"},{"key":"e_1_2_3_29_1","first-page":"106","article-title":"The innervation and properties of the urethral striated muscle","author":"Creed KE","year":"2001","journal-title":"Scand J Urol Nephrol Suppl"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.4.4"},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb16379.x"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002400050061"},{"key":"e_1_2_3_33_1","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":"Andersson KE","year":"1993","journal-title":"Pharmacol Rev"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000473995"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00300786"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000134186.58854.2c"},{"key":"e_1_2_3_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.08.082"},{"key":"e_1_2_3_38_1","article-title":"Urodynamic effects of intravenous and intrathecal administration of E\u2010series prostaglandin 1 receptor antagonist on detrusor overactivity in rats with spinal cord injury","author":"Wada N","year":"2017","journal-title":"Neurourol Urodyn"},{"key":"e_1_2_3_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12080"},{"key":"e_1_2_3_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90373.2008"},{"key":"e_1_2_3_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00275.x"},{"key":"e_1_2_3_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12959"},{"key":"e_1_2_3_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.02.064"},{"key":"e_1_2_3_44_1","article-title":"Effects of an EP2 and EP3 receptor dual agonist, ONO\u20108055, on a radical hysterectomy\u2010Induced underactive bladder model in monkeys","author":"Matsuya H","year":"2017","journal-title":"Low Urin Tract Symptoms"},{"key":"e_1_2_3_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02202011"},{"key":"e_1_2_3_46_1","first-page":"469","article-title":"Urinary incontinence in women: a comprehensive review of the pathophysiology, diagnosis and treatment","volume":"66","author":"Padmanabhan P","year":"2014","journal-title":"Minerva Ginecol"},{"key":"e_1_2_3_47_1","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.4613"},{"key":"e_1_2_3_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.05.136"},{"key":"e_1_2_3_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1123-8"},{"key":"e_1_2_3_50_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2011.546338"},{"key":"e_1_2_3_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12577"},{"key":"e_1_2_3_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2010.02.027"},{"key":"e_1_2_3_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13759"},{"key":"e_1_2_3_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13235"},{"key":"e_1_2_3_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00686.2016"},{"key":"e_1_2_3_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2013.149"},{"key":"e_1_2_3_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00318"},{"key":"e_1_2_3_58_1","first-page":"157","article-title":"Transforming growth factor beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis","volume":"44","author":"Roberts AB","year":"1988","journal-title":"Recent Prog Horm Res"},{"key":"e_1_2_3_59_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/120525"},{"key":"e_1_2_3_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0739-7"},{"key":"e_1_2_3_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.08.008"},{"key":"e_1_2_3_62_1","first-page":"S74","article-title":"The hormone relaxin reverses fibrosis and increases detrusor force generation to rescue fibrotic bladders due to chronic radiation cystitis","volume":"36","author":"Ikeda Y","year":"2017","journal-title":"Neurourol Urodyn"},{"key":"e_1_2_3_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2401"},{"key":"e_1_2_3_64_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/j.2040-4603.2015.tb00596.x","article-title":"Neural control of the lower urinary tract","author":"de Groat WC","year":"2015","journal-title":"Compr Physiol"},{"key":"e_1_2_3_65_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200363230-00003"},{"key":"e_1_2_3_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.01.044"},{"key":"e_1_2_3_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.12.062"},{"key":"e_1_2_3_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.11.039"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnau.23516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.23516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T04:32:11Z","timestamp":1751776331000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.23516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":67,"journal-issue":{"issue":"S4","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/nau.23516"],"URL":"https:\/\/doi.org\/10.1002\/nau.23516","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"value":"0733-2467","type":"print"},{"value":"1520-6777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6]]},"assertion":[{"value":"2017-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}