Linked Life Data

1912294

Source:http://linkedlifedata.com/resource/pubmed/id/1912294

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-11-4
pubmed:abstractText
Evidence that partially oxidized piperidine derivatives such as the Parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are biotransformed in a reaction catalyzed by monoamine oxidase B (MAO-B) to neurotoxic pyridinium metabolites led to studies resulting in the identification of the haloperidol-derived pyridinium metabolite in the urine of drug-treated rats. The present in vitro studies examine the metabolic pathway governing this overall four-electron oxidation. Although haloperidol and its 1,2,3,6-tetrahydropyridine dehydration product were not substrates for purified bovine liver MAO-B, both compounds were biotransformed to the pyridinium product by rat liver microsomal preparations. The dependence on NADPH and the inhibition by SKF-525A argue that one or more liver cytochrome P-450 isozymes may catalyze this transformation. Attempts to detect possible metabolic intermediates were not successful. Chemical model studies, however, suggest that the expected intermediary amino enol and dihydropyridinium species may be too unstable to isolate. The possible significance of this pathway with respect to haloperidol-induced central nervous system dysfunction is considered.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Studies on the in vitro conversion of haloperidol to a potentially neurotoxic pyridinium metabolite.
pubmed:affiliation
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg 24061.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't