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

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Carmo, H (Author) FFUP; Hengstler, JG (Author) Other; de Boer, D (Author) Other; Ringel, M (Author) Other; Carvalho, F (Author) FFUP; Fernandes, E (Author) FFUP; Remiao, F (Author) FFUP; dos Reys, LA (Author) Other; Oesch, F (Author) Other; Bastos, MD (Author) FFUP

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 369

Pages: 198-205

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 33 Citations

Scopus - 39 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-BVC

DOI: 10.1007/s00210-003-0850-0

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8