{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:28:38Z","timestamp":1790872118837,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3561,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptor\u2010mediated contraction of lower urinary tract tissues may, <jats:italic>via<\/jats:italic> a selective relief of outlet obstruction, lead to an improvement in symptoms.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The present study describes the \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor (\u03b1<jats:sub>1<\/jats:sub>\u2010AR) subtype selectivities of two novel \u03b1<jats:sub>1<\/jats:sub>\u2010AR antagonists, Ro\u200370\u20100004 (aka RS\u2010100975) and a structurally\u2010related compound RS\u2010100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second\u2010messenger studies in intact CHO\u2010K1 cells expressing human cloned \u03b1<jats:sub>1A<\/jats:sub>\u2010, \u03b1<jats:sub>1B<\/jats:sub>\u2010 and \u03b1<jats:sub>1D<\/jats:sub>\u2010AR showed nanomolar affinity and significant \u03b1<jats:sub>1A<\/jats:sub>\u2010AR subtype selectivity for both Ro\u200370\u20100004 (pK<jats:sub>i<\/jats:sub> 8.9: 60 and 50 fold selectivity) and RS\u2010100329 (pK<jats:sub>i<\/jats:sub> 9.6: 126 and 50 fold selectivity) over the \u03b1<jats:sub>1B<\/jats:sub>\u2010 and \u03b1<jats:sub>1D<\/jats:sub>\u2010AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Noradrenaline\u2010induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro\u200370\u20100004 (pA<jats:sub>2<\/jats:sub> 8.8 and 8.9), RS\u2010100329 (pA<jats:sub>2<\/jats:sub> 9.2 and 9.2), tamsulosin (pA<jats:sub>2<\/jats:sub> 10.4 and 9.8) and prazosin (pA<jats:sub>2<\/jats:sub> 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing \u03b1<jats:sub>1<\/jats:sub>\u2010AR\u2010mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro\u200370\u20100004 and RS\u2010100329 were approximately 100 fold less potent (pA<jats:sub>2<\/jats:sub> values of 6.8\/6.8 and 7.3\/7.9 in HRA\/RA respectively).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The \u03b1<jats:sub>1A<\/jats:sub>\u2010AR subtype selectivity of Ro\u200370\u20100004 and RS\u2010100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a \u2018uroselective\u2019 agent for the treatment of symptoms associated with benign prostatic hyperplasia.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 252\u2013258; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702541\">10.1038\/sj.bjp.0702541<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702541","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:03:02Z","timestamp":1106942582000},"page":"252-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["<i>In vitro<\/i>\u03b1<sub>1<\/sub>\u2010adrenoceptor pharmacology of Ro 70\u20130004 and RS\u2010100329, novel <i>\u03b1<\/i><sub>1A<\/sub>\u2010adrenoceptor selective antagonists"],"prefix":"10.1111","volume":"127","author":[{"given":"T J","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D R","family":"Blue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D V","family":"Daniels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Elworthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Gever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M S","family":"Kava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Morgans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Padilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Tassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R L","family":"Vimont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Chapple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Chess\u2010Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R M","family":"Eglen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D E","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A P D W","family":"Ford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15875.x"},{"issue":"4","key":"e_1_2_6_4_1","first-page":"190","article-title":"Pharmacological assessment of the \u03b11\u2010adrenoceptor (\u03b11\u2010AR) antagonist tamsulosin","volume":"157","author":"BLUE D.R.","year":"1997","journal-title":"J. Urol."},{"key":"e_1_2_6_5_1","first-page":"345","article-title":"Preclinical pharmacology of a novel \u03b11A\/\u03b11L\u2010adrenoceptor antagonist, RS\u2010100975","volume":"15","author":"BLUE D.R.","year":"1996","journal-title":"Neurourol. Urodynam."},{"key":"e_1_2_6_6_1","first-page":"107P","article-title":"The conscious \u2018reflex\u2010compromised\u2019 rat: a model for evaluating the hypotensive potencies of the \u03b11\u2010adrenoceptor antagonists prazosin, tamsulosin and Ro\u200370\u20100004","volume":"120","author":"BLUE D.R.","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1984.tb02798.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00755-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","unstructured":"BUZELIN J.M. HEBERT M. BLONDIN P.&THE PRAZALF GROUP(1993).Alpha\u2010blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin.Br. J. Urol. 72 922\u2013927.","DOI":"10.1111\/j.1464-410X.1993.tb16298.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1978.tb06210.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1992.tb15733.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_6_13_1","first-page":"360P","article-title":"Functional pharmacological characteristics of human, rat, and rabbit cloned \u03b11A\u2010adrenoceptors expressed in Chinese hamster ovary (CHO\u2010K1) cells","volume":"119","author":"DANIELS D.V.","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(94)90031-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(86)90383-4"},{"key":"e_1_2_6_16_1","first-page":"209","article-title":"RS\u201017053 (N\u2010[2\u2010(2\u2010cyclopropylmethoxyphenoxy)ethyl]\u2003\u2010\u20035\u2003\u2010\u2003chloro\u2010a,a\u2010dimethyl\u20101H\u2010indole\u20103\u2010ethanamine hydrochloride), a selective \u03b11A\u2010adrenoceptor antagonist, displays low affinity for functional \u03b11\u2010adrenoceptors in human prostate: implications for adrenoceptor classification","volume":"49","author":"FORD A.P.D.W.","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90136-8"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701207"},{"key":"e_1_2_6_19_1","first-page":"703","article-title":"The \u03b11\u2010Adrenoceptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human \u03b11C\u2010adrenoceptor subtype","volume":"45","author":"FORRAY C.","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)53216-4"},{"key":"e_1_2_6_21_1","first-page":"125","article-title":"Effector\u2010independent antagonist affinity profile of human cloned \u03b11A\u2010adrenoceptor expressed in Chinese hamster ovary cells (CHO\u2010K1)","volume":"39","author":"GEVER J.R.","year":"1997","journal-title":"Pharmacologist"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17053.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0022-5347(17)51106-4","article-title":"Effects of prazosin in patients with benign prostatic obstruction","volume":"130","author":"HEDLUND H.","year":"1983","journal-title":"Br. J. Urol."},{"key":"e_1_2_6_24_1","first-page":"267","article-title":"International Union of Pharmacology X. Recommendation for Nomenclature of \u03b11\u2010Adrenoceptors","volume":"47","author":"HIEBLE J.P.","year":"1995","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701748"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15480.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90080-4"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)80008-9"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15001.x"},{"key":"e_1_2_6_30_1","first-page":"321","article-title":"Characterisation of \u03b11\u2010adrenoceptor subtypes in rat brain: a reevaluation of [3H]WB4101 and [3H]prazosin binding","volume":"29","author":"MORROW A.L.","year":"1986","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_6_31_1","first-page":"193","volume-title":"\u03b1\u2010Adrenoceptors","author":"MURAMATSU I.","year":"1992"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)35544-1"},{"key":"e_1_2_6_33_1","first-page":"136","article-title":"Structure activity relationships of a series of buspirone analogs at alpha\u20101 adrenoceptors: further evidence that rat aorta alpha\u20101 adrenoceptors are of the alpha\u20101D subtype","volume":"278","author":"SAUSSY D.L.","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00004962"},{"key":"e_1_2_6_35_1","first-page":"1284","article-title":"Pharmacological characterisation of the uroselective alpha\u20101 antagonist Rec\u200315\/2739 (SB\u2003216469): Role of the alpha\u20101L adrenoceptor in tissue selectivity, Part II","volume":"281","author":"TESTA R.","year":"1997","journal-title":"J. Pharm. Exp. Ther."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15403.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13259.x"},{"key":"e_1_2_6_38_1","first-page":"359P","article-title":"Whole cell radioligand binding assay reveals \u03b11L\u2010adrenoceptor (AR) antagonist profile for the human cloned \u03b11A\u2010AR in Chinese hamster ovary (CHO\u2010K1) cells","volume":"119","author":"WILLIAMS T.J.","year":"1996","journal-title":"Br. J. Pharmacol."}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702541","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702541","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T06:39:28Z","timestamp":1695883168000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,5]]}},"alternative-id":["10.1038\/sj.bjp.0702541"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702541","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,5]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}