{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T05:23:50Z","timestamp":1698125030983},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T00:00:00Z","timestamp":1095724800000},"content-version":"vor","delay-in-days":5012,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chirality"],"published-print":{"date-parts":[[1991,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although (\u2212)\u2010(S)\u2010trimetoquinol [1\u2010(3,4,5\u2010trimethoxy\u2010benzyl)\u20106,7\u2010dihydroxy\u20101,2,3,4\u2010tetrahydroisoquinoline; TMQ] is recognized as a potent bronchodilator, (+)\u2010(R)\u2010TMQ is a selective antagonist of human platelet aggregation and serotonin secretion induced by thromboxane A<jats:sub>2<\/jats:sub> (TXA<jats:sub>2<\/jats:sub>) agonists. To confirm the pharmacological actions of TMQ analogs, the interaction of the drugs with TXA<jats:sub>2<\/jats:sub> receptors was examined in human platelets and in a mouse sudden death model. The inhibitory potencies of TMQ analogs (pIC<jats:sub>50<\/jats:sub> values) for displacement of [<jats:sup>3<\/jats:sup>H]SQ 29,548 binding to platelets showed excellent correlation with the respective pIC<jats:sub>50<\/jats:sub> (\u2212log IC<jats:sub>50<\/jats:sub>) values for U46619\u2010induced aggregation (<jats:italic>r<\/jats:italic> = 0.99, <jats:italic>P<\/jats:italic> &lt; 0.01) and serotonin secretion (<jats:italic>r<\/jats:italic> = 0.99, <jats:italic>P<\/jats:italic> &lt; 0.01) in human platelet\u2010rich plasma and for whole blood aggregation (<jats:italic>r<\/jats:italic> = 0.99, <jats:italic>P<\/jats:italic> &lt; 0.01). In each system, the rank order of inhibitory potencies was <jats:italic>rac<\/jats:italic>\u2010iodoTMQ \u2a7e (+)\u2010(R)\u2010TMQ &gt; <jats:italic>rac<\/jats:italic>\u2010TMQ \u226b (\u2212)\u2010(S)\u2010TMQ. Antithrombotic effects of TMQ analogs were evaluated in a mouse sudden death model. In vivo antithrombotic potencies of these compounds were consistent with the in vitro potencies as TXA<jats:sub>2<\/jats:sub> receptor antagonists in platelet systems. Administration of <jats:italic>rac<\/jats:italic>\u2010iodoTMQ, (+)\u2010(R)\u2010TMQ and <jats:italic>rac<\/jats:italic>\u2010TMQ 15 min before the injection of U46619 (800 \u03bcg\/kg, iv) protected mice against U46619\u2010induced sudden death. On the other hand, (\u2212)\u2010(S)\u2010TMQ did not protect animals against death. Protection of U46619\u2010induced cardiopulmonary thrombosis by TMQ analogs was seen at doses of 3\u2013100 mg\/kg. Our findings show that these TMQ analogs act as potent and highly stereospecific TXA<jats:sub>2<\/jats:sub> receptor antagonists in vitro and in vivo.<\/jats:p>","DOI":"10.1002\/chir.530030206","type":"journal-article","created":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T10:06:31Z","timestamp":1105092391000},"page":"112-117","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacologic antagonism of thromboxane A<sub>2<\/sub> receptors by trimetoquinol analogs in vitro and in vivo"],"prefix":"10.1002","volume":"3","author":[{"given":"Yangmee","family":"Shin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl J.","family":"Romstedt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrine","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc W.","family":"Harrold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Gerhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duane D.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Popat N.","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis R.","family":"Feller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,21]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)82177-3"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(81)90093-9"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.17.143"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(75)90353-6"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(76)90494-9"},{"key":"e_1_2_1_7_2","first-page":"193","article-title":"Synthesis and platelet antiaggregatory activity of trimetoquinol analogs as endoperoxide\/thromboxane A2 antagonists","volume":"1","author":"Harrold M.","year":"1987","journal-title":"Drug Design Delivery"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)90663-Q"},{"key":"e_1_2_1_9_2","first-page":"1","article-title":"Effect of trimetoquinol analogs for antagonism and endoperoxide\/thromboxane A2\u2010mediated response in human platelets and rat aorta","volume":"232","author":"Mukhopadhyay A.","year":"1985","journal-title":"J. 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