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

@article{citeulike:3771916, abstract = {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 CYP2D6 (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 CYP2D6 poor metabolizers.}, author = {Carmo, H. and Brulport, M. and Hermes, M. and Oesch, F. and de Boer, D. and Remi\~{a}o, F. and Carvalho, F. and Sch\"{o}n, M. R. and Krebsfaenger, N. and Doehmer, J. and Bastos, M. d. e. . L. and Hengstler, J. G.}, citeulike-article-id = {3771916}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.tox.2006.10.024}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17156908}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17156908}, day = {18}, doi = {10.1016/j.tox.2006.10.024}, issn = {0300-483X}, journal = {Toxicology}, keywords = {4-methylthioamphetamine, 4-mta, 5ht, cyp2d6}, month = {January}, number = {3}, pages = {236--244}, posted-at = {2008-12-11 00:10:26}, priority = {2}, title = {CYP2D6 increases toxicity of the designer drug 4-methylthioamphetamine (4-MTA).}, url = {http://dx.doi.org/10.1016/j.tox.2006.10.024}, volume = {229}, year = {2007} }

TY - JOUR ID - citeulike:3771916 L3 - citeulike-article-id:3771916 N2 - 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 CYP2D6 (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 CYP2D6 poor metabolizers. IS - 3 JF - Toxicology SN - 0300-483X EP - 244 TI - CYP2D6 increases toxicity of the designer drug 4-methylthioamphetamine (4-MTA). VL - 229 SP - 236 KW - 4-methylthioamphetamine KW - 4-mta KW - 5ht KW - cyp2d6 AU - Carmo, H AU - Brulport, M AU - Hermes, M AU - Oesch, F AU - de Boer, D AU - Remião, F AU - Carvalho, F AU - Schön, MR AU - Krebsfaenger, N AU - Doehmer, J AU - Bastos, Mde L AU - Hengstler, JG PY - 2007/01/18/ UR - http://dx.doi.org/10.1016/j.tox.2006.10.024 ER -