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rdf:type |
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lifeskim:mentions |
umls-concept:C0001554,
umls-concept:C0018546,
umls-concept:C0025519,
umls-concept:C0033268,
umls-concept:C0035820,
umls-concept:C0059563,
umls-concept:C0332285,
umls-concept:C0520739,
umls-concept:C0870883,
umls-concept:C1882598,
umls-concept:C2603343
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pubmed:issue |
26
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pubmed:dateCreated |
1996-10-21
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pubmed:abstractText |
The levels of haloperidol (HP) and its pyridinium metabolite HPP+ were estimated in plasma and brain tissues of rats treated i.p. with HP (10 mg/kg). HP and HPP+ levels in plasma decreased linearly during the 0-3 hour period following drug administration. On the other hand, HPP+ levels in brain tissues increased gradually during the same period. HPP+ levels in brain tissues increased further when HP (10 mg/kg) was injected for three consecutive days. The formation of HPP+ also was studied in rat brain mitochondrial and liver microsomal preparations. Enzyme activity responsible for the conversion of HP to HPP+ was not found in brain mitochondria. Liver microsomal enzymes catalyzed the oxidation of HP and its tetrahydropyridine dehydration product HPTP to HPP+ with about the same efficiency. Studies employing several cytochrome P450 inhibitors and anti-cytochrome P450 antibodies were carried out in an effort to identify the forms of cytochrome P450 that are responsible for catalyzing the oxidation of HP and HPTP to HPP+. The formation of HPP+ in liver microsomes was strongly inhibited by ketoconazole and nifedipine and by an anti-CYP3A antibody. These results suggest that formation of HPP+ from HP and HPTP in rat liver microsomes is catalyzed mainly by CYP3A although the participation of other P450 forms cannot be ruled out.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antipsychotic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP2E1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Haloperidol,
http://linkedlifedata.com/resource/pubmed/chemical/Ketoconazole,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/N-(4'-fluorobutyrophenone)-4-(4-chlo...,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridinium Compounds
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0024-3205
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
57
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2439-46
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8847965-Animals,
pubmed-meshheading:8847965-Antibodies,
pubmed-meshheading:8847965-Antipsychotic Agents,
pubmed-meshheading:8847965-Biotransformation,
pubmed-meshheading:8847965-Brain,
pubmed-meshheading:8847965-Chromatography, High Pressure Liquid,
pubmed-meshheading:8847965-Cytochrome P-450 CYP2E1,
pubmed-meshheading:8847965-Cytochrome P-450 Enzyme System,
pubmed-meshheading:8847965-Enzyme Inhibitors,
pubmed-meshheading:8847965-Female,
pubmed-meshheading:8847965-Haloperidol,
pubmed-meshheading:8847965-Injections, Intraperitoneal,
pubmed-meshheading:8847965-Ketoconazole,
pubmed-meshheading:8847965-Male,
pubmed-meshheading:8847965-Microsomes, Liver,
pubmed-meshheading:8847965-Mitochondria,
pubmed-meshheading:8847965-Mixed Function Oxygenases,
pubmed-meshheading:8847965-Nifedipine,
pubmed-meshheading:8847965-Pyridinium Compounds,
pubmed-meshheading:8847965-Rats,
pubmed-meshheading:8847965-Rats, Sprague-Dawley
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pubmed:year |
1995
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pubmed:articleTitle |
Studies on the metabolism of haloperidol (HP): the role of CYP3A in the production of the neurotoxic pyridinium metabolite HPP+ found in rat brain following ip administration of HP.
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pubmed:affiliation |
Faculty of Pharmaceutical Sciences, Kobegakuin University, Kobe, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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