Metabolism of N,N-dialkylated amphetamines, including deprenyl, by CYP2D6 expressed in a human cell line
| Autor: | G. B. Baker, R. T. Coutts, Mimi V. Bach |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
CYP2D6
Chromatography Gas Stereochemistry Health Toxicology and Mutagenesis Metabolite Transfection Toxicology Methylation Biochemistry Isozyme Cell Line Methamphetamine chemistry.chemical_compound Microsomes Selegiline medicine Humans Pharmacology biology Amphetamines Benzphetamine Cytochrome P450 General Medicine Metabolism In vitro Amphetamine Cytochrome P-450 CYP2D6 Models Chemical chemistry Microsome biology.protein medicine.drug |
| Zdroj: | Xenobiotica. 30:297-306 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.1080/004982500237686 |
| Popis: | 1. Five N,N-dialkylated amphetamines, N-methyl-N-propargylamphetamine (deprenyl; DEP), N-benzyl-N-methylamphetamine (benzphetamine; BPA), N-allyl-N-methylamphetamine (AMA), N,N-diallylamphetamine (DAA) and N-methyl-N-propylamphetamine (MPA), were metabolized in vitro with a microsomal preparation from cells expressing human CYP2D6 to determine what influence the N,N-dialkyl substituents had on the extent of N-dealkylation and/or aromatic ring oxidation. 2. The results obtained from experiments with the first two substrates, DEP and BPA, were surprisingly different. Whereas DEP was N-demethylated and N-depropargylated by the CYP2D6 enzyme system, no metabolites were formed from BPA. Subsequently, it was determined that AMA, DAA and MPA also underwent CYP2D6-catalysed N-dealkylation. Both N-methyl- and N-allylamphetamine were identified as products of AMA metabolism; similarly, metabolism of MPA produced both N-methyl- and N-propargylamphetamine, and N-allylamphetamine was the sole metabolite of DAA. 3. No N,N-didealkylated product (i.e. amphetamine) was isolated from incubates of any of the five substrates, and none of the N,N-dialkylated substrates was metabolized to a ring-hydroxylated product. 4. Rates of these CYP2D6-catalysed reactions were dependent on the nature and degree of unsaturation of the N-substituents. |
| Databáze: | OpenAIRE |
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