Linked Life Data

14676987

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

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pubmed-article:14676987pubmed:abstractTextSeveral 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.lld:pubmed
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pubmed-article:14676987pubmed:pagination198-205lld:pubmed
pubmed-article:14676987pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:14676987pubmed:year2004lld:pubmed
pubmed-article:14676987pubmed:articleTitleComparative metabolism of the designer drug 4-methylthioamphetamine by hepatocytes from man, monkey, dog, rabbit, rat and mouse.lld:pubmed
pubmed-article:14676987pubmed:affiliationREQUIMTE, Toxicology Department, Faculty of Pharmacy, Porto University, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal. helenacarmo@ff.up.ptlld:pubmed
pubmed-article:14676987pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:14676987pubmed:publicationTypeComparative Studylld:pubmed
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pubmed-article:14676987pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed