Identification of the Cytochrome P450 Isoenzymes Involved in the Formation of the Main Metabolites of the Designer Drugs DOI, DOB, MDOB, and TMA-2 and Studies on Their Capability to Inhibit CYP2D6

AIMS: 4-Iodo-2,5-dimethoxyamphetamine (DOI), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo2,5-dimethoxymethamphetamine (MDOB), and 2,4,5-trimethoxyamphetamine (TMA-2) are designer drugs which have appeared on the illicit drug market. Meanwhile, DOB and TMA-2 have been scheduled in the German Controlled Substances Act. Because of the various possibilities of interactions between different drugs especially with respect to metabolism the first aim of our study was to identify the cytochrome P450 (CYP) isoenzymes involved in the main metabolic steps of DOI, DOB, MDOB, and TMA-2. The second aim was to check whether these drugs are capable to inhibit CYP2D6, one of the major isoenzymes involved in the metabolism of xenobiotics.