TY  - THES
T1  - Phase II metabolism of 3,4-methylenedioxymethamphetamine : synthesis, analysis, and enantioselective in vitro and in vivo kinetics
A1  - Schwaninger,Andrea Eva
Y1  - 2011/12/13
N2  - In the presented studies, the phase II metabolism of MDMA was investigated in vitro and in vivo. Furthermore, evaluation with respect to a possible stereoselective phase I and II metabolism was performed. The in vitro data indicated that sulfation is the major conjugation step with regioselective preferences for position 3 of DHMA. Both MDMA phase I metabolites, DHMA and HMMA, showed inhibition potential towards dopamine sulfation with IC50 values likely to be reached after recreational MDMA doses. Inhibition of dopamine degradation occurring in the central nervous system could be another reason for the drug-induced irreversible damage to central nerve terminals associated with MDMA consumption. Enantioselectivity was observed for DHMA sulfation and HMMA glucuronidation, but not for HMMA sulfation. In vivo urinary data obtained from 10 participants following controlled placebo, low and high dose MDMA administration supported the results from the in vitro experiments. HMMA sulfate was shown to be the major urinary metabolite providing the longest detection time for MDMA consumption. Enantiomeric ratios of all metabolites showed steady increases of R-isomers as a function of ingestion time which should allow distinguishing between recent or earlier MDMA ingestion, at least after a single MDMA dose. 
KW  - Ecstasy
KW  - Amphetamine
KW  - Stoffwechsel
KW  - In vitro
KW  - In vivo
KW  - Sulfatierung
KW  - Enantioselektivität
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2011/4521
ER  -