Linked Life Data

14676987

Source:http://linkedlifedata.com/resource/pubmed/id/14676987

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-10
pubmed:abstractText
Several cases of death associated with 4-methylthioamphetamine (4-MTA) have raised public concern about the abuse of this designer drug that is usually sold as "Ecstasy" or "Flatliners". Since only very little is known about the metabolism of 4-MTA in humans we performed an in vitro study incubating racemic 4-MTA with primary hepatocytes isolated from three male human donors. Additionally, hepatocytes from male monkey (Cynomolgus), dog (Beagle), rabbit (Chinchilla), rat (Sprague-Dawley), and mouse (CD1) were examined for the metabolism of racemic 4-MTA. We observed that 4-MTA was not extensively metabolised by hepatocytes from all species examined. The main metabolite was identified as 4-methylthiobenzoic acid which, for the first time has been described as a human metabolite. In addition to metabolism we also examined 4-MTA-induced toxicity as evidenced by the ATP cellular content. Interestingly, one of the three human donors showed a dramatically increased sensitivity to the reduction in ATP content induced by 4-MTA. Comparing the species examined, the most extensive formation of 4-methylthiobenzoic acid was observed in the rabbit hepatocytes followed by human, monkey, dog and mouse hepatocytes, whereas no formation of 4-methylthiobenzoic acid was seen in the rat hepatocytes. Toxicity data suggest that rabbit hepatocytes are more resistant to 4-MTA than the other species, which may be due to the more extensive metabolism. In conclusion, we have shown that 4-methylthiobenzoic acid is the main metabolite formed from 4-MTA by human hepatocytes and also by the hepatocytes of the other tested species except the rat. Toxicity data suggest only moderate interspecies differences.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
369
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
198-205
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Comparative metabolism of the designer drug 4-methylthioamphetamine by hepatocytes from man, monkey, dog, rabbit, rat and mouse.
pubmed:affiliation
REQUIMTE, Toxicology Department, Faculty of Pharmacy, Porto University, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal. helenacarmo@ff.up.pt
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't