Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH
The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9)...
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| Veröffentlicht in: | Thrombosis research 1985-12, Vol.40 (5), p.581-596 |
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| container_title | Thrombosis research |
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| creator | DE CLERCK, F XHONNEUX, B TOLLENAERE, J. P JANSSEN, P. A. J |
| description | The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin. |
| doi_str_mv | 10.1016/0049-3848(85)90297-X |
| format | Article |
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P ; JANSSEN, P. A. J</creator><creatorcontrib>DE CLERCK, F ; XHONNEUX, B ; TOLLENAERE, J. P ; JANSSEN, P. A. J</creatorcontrib><description>The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/0049-3848(85)90297-X</identifier><identifier>PMID: 2935970</identifier><identifier>CODEN: THBRAA</identifier><language>eng</language><publisher>New York, NY: Elsevier Science</publisher><subject>Amidines - pharmacology ; Biological and medical sciences ; Blood coagulation. Blood cells ; Blood Platelets - metabolism ; Butyrophenones - pharmacology ; Cyproheptadine - pharmacology ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Hydrogen-Ion Concentration ; Ketanserin ; Kinetics ; Male ; Molecular and cellular biology ; Piperidines - pharmacology ; Platelet ; Platelet Aggregation - drug effects ; Receptors, Serotonin - metabolism ; Serotonin - pharmacology ; Serotonin Antagonists - pharmacology ; Spiperone - pharmacology</subject><ispartof>Thrombosis research, 1985-12, Vol.40 (5), p.581-596</ispartof><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-c42cb9155d494f15250db739072964d86e0f166cf78f012de968850c4524ecd33</citedby><cites>FETCH-LOGICAL-c331t-c42cb9155d494f15250db739072964d86e0f166cf78f012de968850c4524ecd33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8751845$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2935970$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DE CLERCK, F</creatorcontrib><creatorcontrib>XHONNEUX, B</creatorcontrib><creatorcontrib>TOLLENAERE, J. P</creatorcontrib><creatorcontrib>JANSSEN, P. A. J</creatorcontrib><title>Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin.</description><subject>Amidines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. Blood cells</subject><subject>Blood Platelets - metabolism</subject><subject>Butyrophenones - pharmacology</subject><subject>Cyproheptadine - pharmacology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Ketanserin</subject><subject>Kinetics</subject><subject>Male</subject><subject>Molecular and cellular biology</subject><subject>Piperidines - pharmacology</subject><subject>Platelet</subject><subject>Platelet Aggregation - drug effects</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotonin - pharmacology</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Spiperone - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtLAzEUhYMoWqv_QCELEV2M5jlJllIfFQpuKrgLaeaOjs5kxiRd-O_ti64ul_Ods_gQuqDkjhJa3hMiTMG10Dda3hrCjCo-DtCIamUKJhQ7RKM9coJOU_omhCpq5DE6ZoZLo8gI2UcYIFQQPOC-xvkLsAvZffahSR12GX8tOxfw0LoMLWQsi-mc4QgehtzHhBd_-AeyCwliE3AfNgsRnM_N6hmmZ-iodm2C890do_fnp_lkWszeXl4nD7PCc05z4QXzC0OlrIQRNZVMkmqhuCGKmVJUugRS07L0tdI1oawCU2otiReSCfAV52N0vd0dYv-7hJRt1yQPbesC9MtkVSkN5bxcgWIL-tinFKG2Q2w6F_8sJXbt1a6l2bU0q6XdeLUfq9rlbn-56KDal3YiV_nVLnfJu7aOLvgm7TGtJNVC8n9tfn8M</recordid><startdate>19851201</startdate><enddate>19851201</enddate><creator>DE CLERCK, F</creator><creator>XHONNEUX, B</creator><creator>TOLLENAERE, J. P</creator><creator>JANSSEN, P. A. J</creator><general>Elsevier Science</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>19851201</creationdate><title>Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH</title><author>DE CLERCK, F ; XHONNEUX, B ; TOLLENAERE, J. P ; JANSSEN, P. A. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-c42cb9155d494f15250db739072964d86e0f166cf78f012de968850c4524ecd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Amidines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Blood Platelets - metabolism</topic><topic>Butyrophenones - pharmacology</topic><topic>Cyproheptadine - pharmacology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Ketanserin</topic><topic>Kinetics</topic><topic>Male</topic><topic>Molecular and cellular biology</topic><topic>Piperidines - pharmacology</topic><topic>Platelet</topic><topic>Platelet Aggregation - drug effects</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Serotonin - pharmacology</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Spiperone - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DE CLERCK, F</creatorcontrib><creatorcontrib>XHONNEUX, B</creatorcontrib><creatorcontrib>TOLLENAERE, J. P</creatorcontrib><creatorcontrib>JANSSEN, P. A. 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J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>1985-12-01</date><risdate>1985</risdate><volume>40</volume><issue>5</issue><spage>581</spage><epage>596</epage><pages>581-596</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><abstract>The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin.</abstract><cop>New York, NY</cop><pub>Elsevier Science</pub><pmid>2935970</pmid><doi>10.1016/0049-3848(85)90297-X</doi><tpages>16</tpages></addata></record> |
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| ispartof | Thrombosis research, 1985-12, Vol.40 (5), p.581-596 |
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| subjects | Amidines - pharmacology Biological and medical sciences Blood coagulation. Blood cells Blood Platelets - metabolism Butyrophenones - pharmacology Cyproheptadine - pharmacology Female Fundamental and applied biological sciences. Psychology Humans Hydrogen-Ion Concentration Ketanserin Kinetics Male Molecular and cellular biology Piperidines - pharmacology Platelet Platelet Aggregation - drug effects Receptors, Serotonin - metabolism Serotonin - pharmacology Serotonin Antagonists - pharmacology Spiperone - pharmacology |
| title | Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH |
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