Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis
The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited t...
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| Veröffentlicht in: | European journal of pharmacology 1989-04, Vol.163 (2-3), p.253-261 |
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| container_title | European journal of pharmacology |
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| creator | KONDO, K SEO, R NAKA, M KITAGAWA, T WAKITANI, K SAKATA, M KIRA, H OKEGAWA, T KAWASAKI, A |
| description | The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis. |
| doi_str_mv | 10.1016/0014-2999(89)90194-5 |
| format | Article |
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ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/0014-2999(89)90194-5</identifier><identifier>PMID: 2721574</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier</publisher><subject>Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Collagen - antagonists & inhibitors ; Collagen - pharmacology ; Coronary Circulation - drug effects ; Coronary Vessels - physiology ; Dogs ; Electric Stimulation ; Female ; Fibrinolytic Agents ; In Vitro Techniques ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - pharmacology ; Receptors, Prostaglandin - drug effects ; Thromboxane A2 - analogs & derivatives ; Thromboxane A2 - antagonists & inhibitors ; Thromboxane A2 - pharmacology ; Time Factors</subject><ispartof>European journal of pharmacology, 1989-04, Vol.163 (2-3), p.253-261</ispartof><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-5b38dde17386d1e44721897cce5e7df4597a57e7daa28479936cc71ad5e7297f3</citedby><cites>FETCH-LOGICAL-c397t-5b38dde17386d1e44721897cce5e7df4597a57e7daa28479936cc71ad5e7297f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6706968$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2721574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KONDO, K</creatorcontrib><creatorcontrib>SEO, R</creatorcontrib><creatorcontrib>NAKA, M</creatorcontrib><creatorcontrib>KITAGAWA, T</creatorcontrib><creatorcontrib>WAKITANI, K</creatorcontrib><creatorcontrib>SAKATA, M</creatorcontrib><creatorcontrib>KIRA, H</creatorcontrib><creatorcontrib>OKEGAWA, T</creatorcontrib><creatorcontrib>KAWASAKI, A</creatorcontrib><title>Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Collagen - antagonists & inhibitors</subject><subject>Collagen - pharmacology</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary Vessels - physiology</subject><subject>Dogs</subject><subject>Electric Stimulation</subject><subject>Female</subject><subject>Fibrinolytic Agents</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Receptors, Prostaglandin - drug effects</subject><subject>Thromboxane A2 - analogs & derivatives</subject><subject>Thromboxane A2 - antagonists & inhibitors</subject><subject>Thromboxane A2 - pharmacology</subject><subject>Time Factors</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFFrFDEUhYNY6lr9Bwp5EFHo2GRmMjf3sZS2Fkr3RZ9DNrmzjsxOxiQL7Xt_uBm7LiQkcM493PMx9kGKb1LI7kII2VY1In7R-BWFxLZSr9hKasBKgKxfs9XR8oa9Tem3EEJhrU7ZaQ21VNCu2PN135PLiYeerx_WVQNCn3M7lZPtNkxDyouUf1G5Mew24dFOxC_rizmGVCyjnfwwcZp8mCmGx8ETj-RoziGe8zDxebSZRsrcbreRtjYPYUn3__PSkN6xk96Oid4f3jP28-b6x9X36n59e3d1eV-5BiFXatNo70lCozsvqW1LCY3gHCkC37cKwSooX2tr3QJi0zkH0voi1wh9c8Y-v-SW3f_sKWWzG5KjsXSgsE8GNOoOoCvG9sXoSskUqTdzHHY2PhkpzALfLGTNQtZoNP_gG1XGPh7y95sd-ePQgXbRPx10m5wd-2gnN6SjrQPRYaebvzbkjY8</recordid><startdate>19890425</startdate><enddate>19890425</enddate><creator>KONDO, K</creator><creator>SEO, R</creator><creator>NAKA, M</creator><creator>KITAGAWA, T</creator><creator>WAKITANI, K</creator><creator>SAKATA, M</creator><creator>KIRA, H</creator><creator>OKEGAWA, T</creator><creator>KAWASAKI, A</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19890425</creationdate><title>Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis</title><author>KONDO, K ; SEO, R ; NAKA, M ; KITAGAWA, T ; WAKITANI, K ; SAKATA, M ; KIRA, H ; OKEGAWA, T ; KAWASAKI, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-5b38dde17386d1e44721897cce5e7df4597a57e7daa28479936cc71ad5e7297f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Collagen - antagonists & inhibitors</topic><topic>Collagen - pharmacology</topic><topic>Coronary Circulation - drug effects</topic><topic>Coronary Vessels - physiology</topic><topic>Dogs</topic><topic>Electric Stimulation</topic><topic>Female</topic><topic>Fibrinolytic Agents</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Receptors, Prostaglandin - drug effects</topic><topic>Thromboxane A2 - analogs & derivatives</topic><topic>Thromboxane A2 - antagonists & inhibitors</topic><topic>Thromboxane A2 - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KONDO, K</creatorcontrib><creatorcontrib>SEO, R</creatorcontrib><creatorcontrib>NAKA, M</creatorcontrib><creatorcontrib>KITAGAWA, T</creatorcontrib><creatorcontrib>WAKITANI, K</creatorcontrib><creatorcontrib>SAKATA, M</creatorcontrib><creatorcontrib>KIRA, H</creatorcontrib><creatorcontrib>OKEGAWA, T</creatorcontrib><creatorcontrib>KAWASAKI, A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KONDO, K</au><au>SEO, R</au><au>NAKA, M</au><au>KITAGAWA, T</au><au>WAKITANI, K</au><au>SAKATA, M</au><au>KIRA, H</au><au>OKEGAWA, T</au><au>KAWASAKI, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1989-04-25</date><risdate>1989</risdate><volume>163</volume><issue>2-3</issue><spage>253</spage><epage>261</epage><pages>253-261</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>2721574</pmid><doi>10.1016/0014-2999(89)90194-5</doi><tpages>9</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 1989-04, Vol.163 (2-3), p.253-261 |
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| subjects | Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Collagen - antagonists & inhibitors Collagen - pharmacology Coronary Circulation - drug effects Coronary Vessels - physiology Dogs Electric Stimulation Female Fibrinolytic Agents In Vitro Techniques Male Medical sciences Pharmacology. Drug treatments Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - pharmacology Receptors, Prostaglandin - drug effects Thromboxane A2 - analogs & derivatives Thromboxane A2 - antagonists & inhibitors Thromboxane A2 - pharmacology Time Factors |
| title | Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis |
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