{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:30:46Z","timestamp":1790818246510,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","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>Ticlopidine is a well\u2010known anti\u2010platelet agent, but is not active by itself <jats:italic>in vitro<\/jats:italic>. We identified a metabolite with anti\u2010platelet activity, which was generated after incubation of 2\u2010oxo\u2010ticlopidine with phenobarbital\u2010induced rat liver homogenate <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An active moiety (UR\u20104501) was isolated by high\u2010performance liquid chromatography after large\u2010scale preparation of metabolites.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The chemical structure of UR\u20104501 was determined by a combination of liquid chromatography mass\/mass spectrometry (LC\/MS\/MS) and nuclear magnetic resonance (NMR) analysis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>UR\u20104501 produced a concentration\u2010dependent inhibition (3\u2013100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) of ADP (10 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>)\u2010induced human platelet aggregation, whereas 2\u2010oxo\u2010ticlopidine (3\u2013100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) did not elicit inhibitory responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>UR\u20104501 (10\u2013100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) strongly inhibited ADP\u2010 and collagen\u2010induced aggregation and slightly inhibited thrombin\u2010induced aggregation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inhibition of rat washed platelet aggregation by UR\u20104501 (100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) persisted, even after the platelets had been washed twice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that UR\u20104501 is the molecule responsible for the <jats:italic>in vivo<\/jats:italic> activities of ticlopidine.<\/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>, 551\u2013557. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705808\">10.1038\/sj.bjp.0705808<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705808","type":"journal-article","created":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T19:29:52Z","timestamp":1086290992000},"page":"551-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Identification of the active metabolite of ticlopidine from rat <i>in vitro<\/i> metabolites"],"prefix":"10.1111","volume":"142","author":[{"given":"Kenji","family":"Yoneda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryou","family":"Iwamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Kishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Mizukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiko","family":"Mogami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1055\/s-0038-1646487","article-title":"Ticlopidine selectively inhibits human platelet responses to adenosine diphosphate","volume":"66","author":"CATTANEO M.","year":"1991","journal-title":"Thromb. 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