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Carmo H, Hengstler JG, de Boer D, Ringel M, Carvalho F, Fernandes E, Remião F, dos Reys LA, Oesch F, de Lourdes Bastos M. 
“Comparative metabolism of the designer drug 4-methylthioamphetamine by hepatocytes from man, monkey, dog, rabbit, rat and mouse”. 
Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb 10;369(2):198-205.
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.
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