| Investigations on the human hepatic cytochrome P450 isozymes involved in the metabolism of 3,4-methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) enantiomers. | |
| | |
MedLine Citation:
|
PMID: 19576971 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
3,4-Methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) are chiral designer drugs distributed on the illicit drug market and they are also N-dealkyl metabolites of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy, Adam), 3,4-methylenedioxyethylamphetamine (MDEA, Eve), and N-methyl-benzodioxolyl-butanamine (MBDB, Eden), respectively. MDA and BDB are mainly metabolized via demethylenation to the corresponding catecholamines. The aim of the present work was to elucidate the contribution of the relevant human P450s in the demethylenation of the MDA and BDB enantiomers. They were incubated using heterologously expressed human P450s and the corresponding metabolites dihydroxyamphetamine and 1,2-dihydroxy-4-[2-amino-butyl]benzene were determined. Highest contributions to the demethylenation as calculated from the enzyme kinetic data were obtained for CYP2D6 (MDA and BDB) and additionally CYP3A4 in the case of BDB at substrate concentrations corresponding to plasma concentrations of recreational users. A preferred transformation of the S-enantiomer could be observed for the CYP2D6- and CYP3A4-catalyzed reactions. |
| | |
Authors:
|
Markus R Meyer; Frank T Peters; Hans H Maurer |
Publication Detail:
|
Type: In Vitro; Journal Article Date: 2009-07-02 |
Journal Detail:
|
Title: Toxicology letters Volume: 190 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2009 Oct |
Date Detail:
|
Created Date: 2009-08-17 Completed Date: 2009-08-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 54-60 Citation Subset: IM |
Affiliation:
|
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Kirrberger Strasse 1, D-66421 Homburg (Saar), Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
3,4-Methylenedioxyamphetamine
/
analogs & derivatives*,
chemistry,
metabolism*,
pharmacokinetics Antibodies, Monoclonal / pharmacology Cytochrome P-450 Enzyme System / antagonists & inhibitors, metabolism* Enzyme Inhibitors / pharmacology Gas Chromatography-Mass Spectrometry Humans Kinetics Microsomes, Liver / drug effects*, enzymology N-Methyl-3,4-methylenedioxyamphetamine / chemistry, metabolism*, pharmacokinetics Stereoisomerism Street Drugs / chemistry, metabolism*, pharmacokinetics |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Enzyme Inhibitors; 0/Street Drugs; 103818-46-8/N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; 42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine; 4764-17-4/3,4-Methylenedioxyamphetamine; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Chloroacetonitrile induces oxidative stress and apoptosis in mouse fetal liver.
Next Document: Development of a new topical system: drug-in-cyclodextrin-in-deformable liposome.