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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

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

Revista

Título: Toxicology

Vol. 229

Páginas: 236-244

ISSN: 0300-483X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 24 Citações

Scopus - 25 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9