Competitive inhibition of sparteine oxidation in human liver by β-adrenoceptor antagonists and other cardiovascular drugs
The rate of oxidation of sparteine by the 9000 × g supernatant fraction of a human liver was measured in the presence of various drugs which exert cardiovascular effects. Hexamethonium, ouabain, caffeine and isoproterenol had no effect on this rate, while alprenolol, metoprolol, oxprenolol, proprano...
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| Veröffentlicht in: | Life sciences (1973) 1984-01, Vol.34 (1), p.73-80 |
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| creator | Otton, S.V. Inaba, T. Kalow, W. |
| description | The rate of oxidation of sparteine by the 9000 × g supernatant fraction of a human liver was measured in the presence of various drugs which exert cardiovascular effects. Hexamethonium, ouabain, caffeine and isoproterenol had no effect on this rate, while alprenolol, metoprolol, oxprenolol, propranolol, timolol, pindolol, lidocaine, mexiletine, 17-n-pentyl-sparteine, tolazoline, quinine, quinidine, cinchonine and cinchonidine inhibited the in vitro reaction competitively. Stereoselective inhibition was observed between quinine (Ki = 15
μM) and quinidine (Ki = 0.06
μM). Genetic evidence suggests that the primary metabolism of sparteine depends on a single species of cytochrome P450. In vitro competitive inhibition of sparteine oxidation by a drug indicates that this drug is capable of occupying the same enzymatic site as sparteine. This may mean that the competing drug is also metabolized at that site and thereby subject to the same genetic variation as sparteine's oxidation; absence of inhibition excludes this possibility. |
| doi_str_mv | 10.1016/0024-3205(84)90332-1 |
| format | Article |
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μM) and quinidine (Ki = 0.06
μM). Genetic evidence suggests that the primary metabolism of sparteine depends on a single species of cytochrome P450. In vitro competitive inhibition of sparteine oxidation by a drug indicates that this drug is capable of occupying the same enzymatic site as sparteine. This may mean that the competing drug is also metabolized at that site and thereby subject to the same genetic variation as sparteine's oxidation; absence of inhibition excludes this possibility.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/0024-3205(84)90332-1</identifier><identifier>PMID: 6141510</identifier><identifier>CODEN: LIFSAK</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Adrenergic beta-Agonists - pharmacology ; Biological and medical sciences ; Cardiovascular Agents - pharmacology ; General pharmacology ; Humans ; Kinetics ; Liver - drug effects ; Liver - metabolism ; Medical sciences ; Oxidation-Reduction - drug effects ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Quinidine - pharmacology ; Quinine - pharmacology ; Sparteine - metabolism</subject><ispartof>Life sciences (1973), 1984-01, Vol.34 (1), p.73-80</ispartof><rights>1984</rights><rights>1984 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-ceebe5032e4b13fb5548b347c3f6b2a326eeb84634aa9f0ff5085d228447311f3</citedby><cites>FETCH-LOGICAL-c386t-ceebe5032e4b13fb5548b347c3f6b2a326eeb84634aa9f0ff5085d228447311f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0024-3205(84)90332-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=9715851$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6141510$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Otton, S.V.</creatorcontrib><creatorcontrib>Inaba, T.</creatorcontrib><creatorcontrib>Kalow, W.</creatorcontrib><title>Competitive inhibition of sparteine oxidation in human liver by β-adrenoceptor antagonists and other cardiovascular drugs</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>The rate of oxidation of sparteine by the 9000 × g supernatant fraction of a human liver was measured in the presence of various drugs which exert cardiovascular effects. Hexamethonium, ouabain, caffeine and isoproterenol had no effect on this rate, while alprenolol, metoprolol, oxprenolol, propranolol, timolol, pindolol, lidocaine, mexiletine, 17-n-pentyl-sparteine, tolazoline, quinine, quinidine, cinchonine and cinchonidine inhibited the in vitro reaction competitively. Stereoselective inhibition was observed between quinine (Ki = 15
μM) and quinidine (Ki = 0.06
μM). Genetic evidence suggests that the primary metabolism of sparteine depends on a single species of cytochrome P450. In vitro competitive inhibition of sparteine oxidation by a drug indicates that this drug is capable of occupying the same enzymatic site as sparteine. This may mean that the competing drug is also metabolized at that site and thereby subject to the same genetic variation as sparteine's oxidation; absence of inhibition excludes this possibility.</description><subject>Adrenergic beta-Agonists - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular Agents - pharmacology</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Medical sciences</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinidine - pharmacology</subject><subject>Quinine - pharmacology</subject><subject>Sparteine - metabolism</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1984</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM-OFCEQh4nRrLOrb6AJB2PWQys00E1fNjET_yWbeNEzoaHYwXRDC_TE9bF8EJ9JZmcyR09VqfrqF_gQekHJW0po946QljesJeJa8jcDYaxt6CO0obIfGtIx-hhtzshTdJnzD0KIED27QBcd5VRQskG_t3FeoPji94B92PmxtjHg6HBedCrgA-D4y1v9MPYB79ZZBzxVPuHxHv_902ibIEQDS4kJ61D0XQw-l1x7i2PZVdDoZH3c62zWSSds03qXn6EnTk8Znp_qFfr-8cO37efm9uunL9v3t41hsiuNARhBENYCHylzoxBcjoz3hrlubDVruwpI3jGu9eCIc4JIYdtWct4zSh27Qq-PuUuKP1fIRc0-G5gmHSCuWUkysJ51ooL8CJoUc07g1JL8rNO9okQdlKuDT3XwqSRXD8oVrWcvT_nrOIM9H50c1_2r075-X08u6WB8PmNDT4UUh5ibIwbVxd5DUtl4CAasT2CKstH__x3_AP5tn-s</recordid><startdate>19840102</startdate><enddate>19840102</enddate><creator>Otton, S.V.</creator><creator>Inaba, T.</creator><creator>Kalow, W.</creator><general>Elsevier Inc</general><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>19840102</creationdate><title>Competitive inhibition of sparteine oxidation in human liver by β-adrenoceptor antagonists and other cardiovascular drugs</title><author>Otton, S.V. ; Inaba, T. ; Kalow, W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-ceebe5032e4b13fb5548b347c3f6b2a326eeb84634aa9f0ff5085d228447311f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>Adrenergic beta-Agonists - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular Agents - pharmacology</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Medical sciences</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinidine - pharmacology</topic><topic>Quinine - pharmacology</topic><topic>Sparteine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Otton, S.V.</creatorcontrib><creatorcontrib>Inaba, T.</creatorcontrib><creatorcontrib>Kalow, W.</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>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Otton, S.V.</au><au>Inaba, T.</au><au>Kalow, W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Competitive inhibition of sparteine oxidation in human liver by β-adrenoceptor antagonists and other cardiovascular drugs</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>1984-01-02</date><risdate>1984</risdate><volume>34</volume><issue>1</issue><spage>73</spage><epage>80</epage><pages>73-80</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><coden>LIFSAK</coden><abstract>The rate of oxidation of sparteine by the 9000 × g supernatant fraction of a human liver was measured in the presence of various drugs which exert cardiovascular effects. Hexamethonium, ouabain, caffeine and isoproterenol had no effect on this rate, while alprenolol, metoprolol, oxprenolol, propranolol, timolol, pindolol, lidocaine, mexiletine, 17-n-pentyl-sparteine, tolazoline, quinine, quinidine, cinchonine and cinchonidine inhibited the in vitro reaction competitively. Stereoselective inhibition was observed between quinine (Ki = 15
μM) and quinidine (Ki = 0.06
μM). Genetic evidence suggests that the primary metabolism of sparteine depends on a single species of cytochrome P450. In vitro competitive inhibition of sparteine oxidation by a drug indicates that this drug is capable of occupying the same enzymatic site as sparteine. This may mean that the competing drug is also metabolized at that site and thereby subject to the same genetic variation as sparteine's oxidation; absence of inhibition excludes this possibility.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>6141510</pmid><doi>10.1016/0024-3205(84)90332-1</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0024-3205 |
| ispartof | Life sciences (1973), 1984-01, Vol.34 (1), p.73-80 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adrenergic beta-Agonists - pharmacology Biological and medical sciences Cardiovascular Agents - pharmacology General pharmacology Humans Kinetics Liver - drug effects Liver - metabolism Medical sciences Oxidation-Reduction - drug effects Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Quinidine - pharmacology Quinine - pharmacology Sparteine - metabolism |
| title | Competitive inhibition of sparteine oxidation in human liver by β-adrenoceptor antagonists and other cardiovascular drugs |
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