• DOI:10.1007/s00210-003-0850-0
• Corpus ID: 35836705

Comparative metabolism of the designer drug 4-methylthioamphetamine by hepatocytes from man, monkey, dog, rabbit, rat and mouse

@article{Carmo2003ComparativeMO,
  title={Comparative metabolism of the designer drug 4-methylthioamphetamine by hepatocytes from man, monkey, dog, rabbit, rat and mouse},
  author={Helena Carmo and Jan G. Hengstler and Douwe de Boer and Michael T. Ringel and F{\'e}lix Carvalho and Eduarda Fernandes and Fernando Remi{\~a}o and Lesseps A. dos Reys and Franz Oesch and Maria Lourdes Bastos},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2003},
  volume={369},
  pages={198-205}
}

• H. Carmo, J. Hengstler, +7 authors Maria Lourdes Bastos
• Published 1 February 2004
• Biology, Medicine
• Naunyn-Schmiedeberg's Archives of Pharmacology

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.