Linked Life Data

9114984

Source:http://linkedlifedata.com/resource/pubmed/id/9114984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-6-23
pubmed:abstractText
3-Carbamoyl-2-phenylpropionaldehyde has recently been proposed [Thompson et al. (1996) Chem. Res. Toxicol. 9, 1225-1229] as a potential reactive metabolite of the anti-epileptic drug felbamate. This aldehyde was found to undergo rapid elimination to generate 2-phenylpropenal and reversible cyclization to generate 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one at physiological pH. 2-Phenylpropenal, an alpha,beta-unsaturated aldehyde commonly termed atropaldehyde, is a potent electrophile and undergoes rapid conjugation with glutathione. We sought to demonstrate the formation of atropaldehyde in vivo through the identification of mercapturic acids in rat and human urine after felbamate administration. In this paper, we describe the identification of both the reduced (N-acetyl-S-(2-phenylpropan-3-ol)-L-cysteine) and oxidized (N-acetyl-S-(2-phenyl-3-propanoic acid)-L-cysteine) mercapturic acids of atropaldehyde in rat and human urine. The reduced species was the more abundant in human (approximately 2:1) and rat (approximately 6:1) urine. These findings establish the possibility that atropaldehyde is formed from felbamate in vivo, undergoes glutathione conjugation, and is ultimately excreted in urine in the form of mercapturic acids. Thus, the proposed pathway of felbamate biotransformation, if confirmed in patients, could contribute to our understanding of the toxicities observed during felbamate treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
457-62
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Identification of modified atropaldehyde mercapturic acids in rat and human urine after felbamate administration.
pubmed:affiliation
Chemistry Department, University of Virginia, Charlottesville 22901, USA.
pubmed:publicationType
Journal Article