TY  - THES
T1  - Enantiomers of methylenedioxy designer drugs : the role of cytochrome P450s and catechol-O-methyltransferase in their metabolism
A1  - Meyer,Markus Robert
Y1  - 2009/08/13
N2  - In the presented studies, the CYP dependent, enantioselective N-dealkylation and demethylenation of the designer drugs MDMA (Ecstasy), MBDB (Eden), and MDEA (Eve) was investigated. Furthermore, the COMT-catalyzed O-methylation of the supposed neurotoxic catecholic metabolites of the aforementioned drugs and the demethylenation of the dealkyl metabolites MDA and BDB was studied. The data clearly indicated a metabolic preference for the S-enantiomer of all investigated compounds, indicating CYP2C19 to be the most selective in all cases. Furthermore, their N-dealkyl-metabolites MDA, BDB are also demethylenated with a preference for their S-enantiomers. Data also suggest that the primary amines are not metabolized as enantioselectively as the secondary amines. The catecholic phase-I metabolites are also enantioselectively methylated with a preference for their S-enantiomer. These findings explain in part the observed different in vivo kinetic of these methylenedioxy designer drugs. Inhibition studies with the catecholic phase-I metabolites DHMA, DHEA, and DHMBB indicated an uncompetitive inhibition of the sCOMT catalyzed dopamine 3-methylation. This inhibition of the dopamine methylation in the central nervous system could be another reason for the drug-induced irreversible damage to central nerve terminals.
KW  - Cytochrome
KW  - Drogenmissbrauch
KW  - Metabolismus
KW  - Catecholmethyltransferase <Catechol-0-Methyltransferase>
KW  - Enantiomere
KW  - Ecstasy
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2009/2400
ER  -