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Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives.
Bach, M V; Coutts, R T; Baker, G B.
Affiliation
  • Bach MV; Neurochemical Research Unit, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Xenobiotica ; 29(7): 719-32, 1999 Jul.
Article de En | MEDLINE | ID: mdl-10456690
ABSTRACT
1. Amphetamine (AM) and five amphetamine derivatives, N-ethylamphetamine (NEA), N-butylamphetamine (NBA), 4-methoxyamphetamine (M-AM), 4-methoxy-N-ethylamphetamine (M-NEA) and 4-methoxy-N-butylamphetamine (M-NBA) were incubated with microsomal preparations from cells expressing human CYP2D6 to determine whether the enzyme was capable of catalyzing the direct ring oxidation of all substrates; the N-dealkylation of NEA, NBA, M-NEA and M-NBA; and the O-demethylation of M-AM, M-NEA and M-NBA. 2. None of the six compounds examined was N-dealkylated to any extent. 3. The only metabolites produced from AM, NEA and NBA were the corresponding ring 4-hydroxylated compounds, and the rates of formation were low. 4. All ring 4-methoxylated substrates were efficiently O-demethylated by CYP2D6 to their corresponding phenols. The size of the N-alkyl group influenced the rates of formation of these phenolamines. In contrast to reported findings with 2- and 3-methoxyamphetamines, none of the 4-methoxyamphetamines was ring-oxidized in the CYP2D6 enzyme system to 2- or 3-hydroxy-4-methoxyamphetamines or to dihydroxyamphetamines.
Sujet(s)
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Collection: 01-internacional Base de données: MEDLINE Sujet principal: Cytochrome P-450 CYP2D6 / Amfétamine Limites: Humans Langue: En Journal: Xenobiotica Année: 1999 Type de document: Article Pays d'affiliation: Canada
Recherche sur Google
Collection: 01-internacional Base de données: MEDLINE Sujet principal: Cytochrome P-450 CYP2D6 / Amfétamine Limites: Humans Langue: En Journal: Xenobiotica Année: 1999 Type de document: Article Pays d'affiliation: Canada
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