CYP2D6 increases toxicity of the designer drug 4-methylthioamphetamine (4-MTA)

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Helena Carmo (Author) FFUP; Marc Brulport (Author) Other; Matthias Hermes (Author) Other; Franz Oesch (Author) Other; Douwe de Boer (Author) Other; Fernando Remiao (Author) FFUP; Felix Carvalho (Author) FFUP; Michael R Schoen (Author) Other; Niels Krebsfaenger (Author) Other; Johannes Doehmer (Author) Other; Maria de Lourdes Bastos (Author) FFUP; Jan G Hengstler (Author) Other

Journal

Title: Toxicology

Vol. 229

Pages: 236-244

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 25 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-C7Q

DOI: 10.1016/j.tox.2006.10.024

Abstract (EN): 4-Methylthioamphetamine (4-MTA) belongs to a group of new amphetamine derivatives that is usually sold as "ecstasy" or "flatliners" on the illicit drug market. Large interindividual differences in 4-MTA mediated toxicity have been reported in humans. Therefore, we tested whether CYP2D6 or its variant alleles as well as CYP3A4 influence the susceptibility to 4-MTA. For this purpose, we used the colony formation assay with Chinese hamster lung fibroblast V79 cells expressing human wild-type CYP2136 (CYP2D6*1), the low activity alleles CYP2D6*2, CYP2D6*9, as well as human CYP3A4. The obtained results showed that the expression of wild type CYP2D6*1 clearly enhanced the susceptibility to the cytotoxic effects of 4-MTA compared with the parental cells devoid of CYP-dependent enzymatic activity. Toxicity in V79 CYP2D6*1 was also higher compared to the V79 cell lines expressing the low activity alleles CYP2D6*2 and CYP2D6*9. In contrast to CYP2D6, the CYP3A4 isoenzyme did not enhance 4-MTA toxicity. In conclusion, our results suggest that CYP2D6 rapid metabolizers may be more susceptible to 4-MTA toxicity than CYP2136 poor metabolizers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9