{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:20:17Z","timestamp":1791069617220,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1569,"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":[[2004,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Tegaserod (Zelnorm\u00ae) is a potent 5\u2010hydroxytryptamine<jats:sub>4<\/jats:sub> (5\u2010HT<jats:sub>4<\/jats:sub>) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5\u2010HT<jats:sub>2<\/jats:sub> receptors, and compared its potency in this respect to its 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonist activity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tegaserod had significant binding affinity for human recombinant 5\u2010HT<jats:sub>2A<\/jats:sub>, 5\u2010HT<jats:sub>2B<\/jats:sub> and 5\u2010HT<jats:sub>2C<\/jats:sub> receptors (p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>=7.5, 8.4 and 7.0, respectively). The 5\u2010HT<jats:sub>2B<\/jats:sub> receptor\u2010binding affinity of tegaserod was identical to that at human recombinant 5\u2010HT<jats:sub>4(c)<\/jats:sub> receptors (mean p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>=8.4) in human embryonic kidney\u2010293 (HEK\u2010293) cells stably transfected with the human 5\u2010HT<jats:sub>4(c)<\/jats:sub> receptor.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tegaserod (0.1\u20133 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) inhibited 5\u2010HT\u2010mediated contraction of the rat isolated stomach fundus potently (p<jats:italic>A<\/jats:italic><jats:sub>2<\/jats:sub>=8.3), consistent with 5\u2010HT<jats:sub>2B<\/jats:sub> receptor antagonist activity. Tegaserod produced, with similar potency, an elevation of adenosine 3\u2032,5\u2032 cyclic monophosphate in HEK\u2010293 cells stably transfected with the human 5\u2010HT<jats:sub>4(c)<\/jats:sub> receptor (mean pEC<jats:sub>50<\/jats:sub>=8.6), as well as 5\u2010HT<jats:sub>4<\/jats:sub> receptor\u2010mediated relaxation of the rat isolated oesophagus (mean pEC<jats:sub>50<\/jats:sub>=8.2) and contraction of the guinea\u2010pig isolated colon (mean pEC<jats:sub>50<\/jats:sub>=8.3).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Following subcutaneous administration, tegaserod (0.3 or 1 mg kg<jats:sup>\u22121<\/jats:sup>) inhibited contractions of the stomach fundus in anaesthetized rats in response to intravenous dosing of <jats:italic>\u03b1<\/jats:italic>\u2010methyl 5\u2010HT (0.03 mg kg<jats:sup>\u22121<\/jats:sup>) and BW 723C86 (0.3 mg kg<jats:sup>\u22121<\/jats:sup>), selective 5\u2010HT<jats:sub>2B<\/jats:sub> receptor agonists. At similar doses, tegaserod (1 and 3 mg kg<jats:sup>\u22121<\/jats:sup> subcutaneously) evoked a 5\u2010HT<jats:sub>4<\/jats:sub> receptor\u2010mediated increase in colonic transit in conscious guinea\u2010pigs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data from this study indicate that tegaserod antagonizes 5\u2010HT<jats:sub>2B<\/jats:sub> receptors at concentrations similar to those that activate 5\u2010HT<jats:sub>4<\/jats:sub> receptors. It remains to be determined whether this 5\u2010HT<jats:sub>2B<\/jats:sub> receptor antagonist activity of tegaserod contributes to its clinical profile.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 549\u2013560. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705929\">10.1038\/sj.bjp.0705929<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705929","type":"journal-article","created":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T22:33:50Z","timestamp":1099002830000},"page":"549-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["The 5\u2010HT<sub>4<\/sub> receptor agonist, tegaserod, is a potent 5\u2010HT<sub>2B<\/sub> receptor antagonist <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1111","volume":"143","author":[{"given":"D T","family":"Beattie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A M","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Marquess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R G","family":"Vickery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S R","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Pulido\u2010Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"McCullough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Sandlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P P A","family":"Humphrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01297028"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280000239"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00928.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(96)00087-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1995.tb05850.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14977.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702632"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00466-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704571"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01087-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00013a010"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2001.00925.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01449.x"},{"key":"e_1_2_7_16_1","first-page":"44","article-title":"Cisapride in the management of chronic functional dyspepsia: a multicenter, double\u2010blind, placebo\u2010controlled study","volume":"10","author":"DERUYTTERE M.","year":"1987","journal-title":"Clin. 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