{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:41:29Z","timestamp":1773661289301,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1703,"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":[[2004,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The <jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub>\u2010adrenoceptor antagonist properties of the <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptor nonconventional partial agonist, CGP 12177A, was investigated in functional assays in rat aorta and in radioligand binding assays in rat cerebral cortical membranes. In addition, binding affinities of other <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptor ligands were measured to investigate any correlation between <jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub>\u2010adrenoceptor affinity and relaxant potency in phenylephrine\u2010constricted rings.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In functional studies, CGP 12177A produced parallel rightward shifts of the phenylephrine CRC with no reduction in the maximum responses. Schild regression analysis gave a straight line with a slope of 0.95 (95% CL: 0.87\u20131.04), suggesting reversible competitive antagonism, and gave a p<jats:italic>K<\/jats:italic><jats:sub>B<\/jats:sub> value of 5.26. In contrast, CGP 12177A (300 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) had no effect on contraction induced by the thromboxane\u2010mimetic, U46619.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In binding studies, CGP 12177A competed monophasically with [<jats:sup>3<\/jats:sup>H]prazosin binding (Hill slope, 0.95, 95% CL: 0.76\u20131.13), giving a p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> value of 5.48, in good agreement with the p<jats:italic>K<\/jats:italic><jats:sub>B<\/jats:sub> from functional studies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Competition experiments with various other <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptor ligands showed that they all displaced [<jats:sup>3<\/jats:sup>H]prazosin in a manner consistent with one\u2010site competition. p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values were as follows: SR 59230A, 6.25; cyanopindolol, 6.33; bupranolol, 6.35; alprenolol, 5.90; propranolol, 5.80; BRL 37344, 5.50; ICI 118551, 5.55; CGP 20712A, 5.26. The p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values correlated well with the pEC<jats:sub>50<\/jats:sub> values for relaxation of phenylephrine\u2010constricted rat aorta obtained previously (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>=0.984, <jats:italic>P<\/jats:italic>&lt;0.0001).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, relaxant effects of CGP 12177A and other <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptor ligands in phenylephrine\u2010constricted rat aorta can be attributed to <jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub>\u2010adrenoceptor blockade and are unrelated to effects at <jats:italic>\u03b2<\/jats:italic><jats:sub>3<\/jats:sub>\u2010adrenoceptors or atypical <jats:italic>\u03b2<\/jats:italic>\u2010adrenoceptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>142<\/jats:bold>, 781\u2013787. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705840\">10.1038\/sj.bjp.0705840<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705840","type":"journal-article","created":{"date-parts":[[2004,6,17]],"date-time":"2004-06-17T17:18:11Z","timestamp":1087492691000},"page":"781-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["<i>\u03b1<\/i><sub>1<\/sub>\u2010Adrenoceptor antagonist properties of CGP 12177A and other <i>\u03b2<\/i>\u2010adrenoceptor ligands: evidence against <i>\u03b2<\/i><sub>3<\/sub>\u2010 or atypical <i>\u03b2<\/i>\u2010adrenoceptors in rat aorta"],"prefix":"10.1111","volume":"142","author":[{"given":"Nataraj","family":"Brahmadevara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus M","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/309163a0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00094a025"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705017"},{"key":"e_1_2_7_7_1","article-title":"\u03b1\n                  1\u2010adrenoceptor antagonist properties of the \u03b2\u2010adrenoceptor non\u2010conventional partial agonist CGP 12177A","author":"BRAHMADEVARA N.","year":"2003","journal-title":"Proceedings of the Pharmacological Society at"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703091"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200308000-00012"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2570461"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00501307"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701523"},{"key":"e_1_2_7_14_1","first-page":"35","article-title":"Evidence for a sympathetic alpha receptor blocking action of beta receptor blocking agents","volume":"166","author":"GULATI O.D.","year":"1968","journal-title":"J. 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