Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man
1. Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance w...
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| Veröffentlicht in: | British journal of clinical pharmacology 1991-09, Vol.32 (3), p.295-302 |
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| creator | Ladona, MG Lindstrom, B Thyr, C Dun‐Ren, P Rane, A |
| description | 1. Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti‐human P450 IID6 (MAb 114/2) and anti‐rat P450 IIIA (PCN 2‐13‐1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N‐demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2‐13‐1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N‐demethylase activities. |
| doi_str_mv | 10.1111/j.1365-2125.1991.tb03902.x |
| format | Article |
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Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti‐human P450 IID6 (MAb 114/2) and anti‐rat P450 IIIA (PCN 2‐13‐1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N‐demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2‐13‐1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N‐demethylase activities.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/j.1365-2125.1991.tb03902.x</identifier><identifier>PMID: 1838002</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Antibodies, Monoclonal ; Blotting, Western ; Chromatography, High Pressure Liquid ; Codeine - metabolism ; Cytochrome P-450 CYP2D6 ; Cytochrome P-450 Enzyme System - metabolism ; Dehydroepiandrosterone - pharmacology ; Dextromethorphan - metabolism ; Embryonic and Fetal Development ; Humans ; Methylation ; Microsomes, Liver - enzymology ; Microsomes, Liver - metabolism ; Midazolam - pharmacology ; Mixed Function Oxygenases - metabolism</subject><ispartof>British journal of clinical pharmacology, 1991-09, Vol.32 (3), p.295-302</ispartof><rights>1991 The British Pharmacological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3922-cb57585a837256f826cac04764aa5fe81a97d3a05b77f13dab640b217f377d313</citedby><cites>FETCH-LOGICAL-c3922-cb57585a837256f826cac04764aa5fe81a97d3a05b77f13dab640b217f377d313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1838002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ladona, MG</creatorcontrib><creatorcontrib>Lindstrom, B</creatorcontrib><creatorcontrib>Thyr, C</creatorcontrib><creatorcontrib>Dun‐Ren, P</creatorcontrib><creatorcontrib>Rane, A</creatorcontrib><title>Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>1. Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti‐human P450 IID6 (MAb 114/2) and anti‐rat P450 IIIA (PCN 2‐13‐1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N‐demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2‐13‐1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N‐demethylase activities.</description><subject>Antibodies, Monoclonal</subject><subject>Blotting, Western</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Codeine - metabolism</subject><subject>Cytochrome P-450 CYP2D6</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Dehydroepiandrosterone - pharmacology</subject><subject>Dextromethorphan - metabolism</subject><subject>Embryonic and Fetal Development</subject><subject>Humans</subject><subject>Methylation</subject><subject>Microsomes, Liver - enzymology</subject><subject>Microsomes, Liver - metabolism</subject><subject>Midazolam - pharmacology</subject><subject>Mixed Function Oxygenases - metabolism</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVUU1v1DAQtRBV2RZ-AlLUA7cEf6zjpAdQu5RSqaIc4GxNkjHxKrEXJ1t2b_yE_sb-kjrdVQtH5jIjvzdvxvMIOWE0YzHeLzMmcplyxmXGypJlY0VFSXm2eUFmT9BLMqOC5qnkkr0iR8OwpJQJlstDcsgKUVDKZ6T9ZI3BgG600CXG4xhTg7fY-VUfXxNvkrHF5Ob-z10Crkm-xqLBHsd228FovZsYtW_QOnwkNLgZg58IPqxacIl1SQ_uNTkw0A34Zp-PyY_PF98XX9Lrm8urxdl1WouS87SupJKFhEIoLnNT8LyGms5VPgeQBgsGpWoEUFkpZZhooMrntOJMGaEiwMQx-bDTXa2rHps6_iFAp1fB9hC22oPV_yLOtvqnv9XxboXkk8C7vUDwv9Y4jLq3Q41dBw79etCK55zH3SLxdEesgx-GgOZpCKN68kkvJ1GpJzP05JPe-6Q3sfnt32s-t-6MifjHHf7bdrj9D2V9vvg2VeIB7NqmvA</recordid><startdate>199109</startdate><enddate>199109</enddate><creator>Ladona, MG</creator><creator>Lindstrom, B</creator><creator>Thyr, C</creator><creator>Dun‐Ren, P</creator><creator>Rane, A</creator><general>Blackwell Publishing Ltd</general><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><scope>5PM</scope></search><sort><creationdate>199109</creationdate><title>Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man</title><author>Ladona, MG ; Lindstrom, B ; Thyr, C ; Dun‐Ren, P ; Rane, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3922-cb57585a837256f826cac04764aa5fe81a97d3a05b77f13dab640b217f377d313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Antibodies, Monoclonal</topic><topic>Blotting, Western</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Codeine - metabolism</topic><topic>Cytochrome P-450 CYP2D6</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Dehydroepiandrosterone - pharmacology</topic><topic>Dextromethorphan - metabolism</topic><topic>Embryonic and Fetal Development</topic><topic>Humans</topic><topic>Methylation</topic><topic>Microsomes, Liver - enzymology</topic><topic>Microsomes, Liver - metabolism</topic><topic>Midazolam - pharmacology</topic><topic>Mixed Function Oxygenases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ladona, MG</creatorcontrib><creatorcontrib>Lindstrom, B</creatorcontrib><creatorcontrib>Thyr, C</creatorcontrib><creatorcontrib>Dun‐Ren, P</creatorcontrib><creatorcontrib>Rane, A</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ladona, MG</au><au>Lindstrom, B</au><au>Thyr, C</au><au>Dun‐Ren, P</au><au>Rane, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>1991-09</date><risdate>1991</risdate><volume>32</volume><issue>3</issue><spage>295</spage><epage>302</epage><pages>295-302</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>1. Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti‐human P450 IID6 (MAb 114/2) and anti‐rat P450 IIIA (PCN 2‐13‐1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N‐demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2‐13‐1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N‐demethylase activities.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>1838002</pmid><doi>10.1111/j.1365-2125.1991.tb03902.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0306-5251 |
| ispartof | British journal of clinical pharmacology, 1991-09, Vol.32 (3), p.295-302 |
| issn | 0306-5251 1365-2125 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antibodies, Monoclonal Blotting, Western Chromatography, High Pressure Liquid Codeine - metabolism Cytochrome P-450 CYP2D6 Cytochrome P-450 Enzyme System - metabolism Dehydroepiandrosterone - pharmacology Dextromethorphan - metabolism Embryonic and Fetal Development Humans Methylation Microsomes, Liver - enzymology Microsomes, Liver - metabolism Midazolam - pharmacology Mixed Function Oxygenases - metabolism |
| title | Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man |
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