Microsomal formation and chemical decomposition of pargyline N-oxide |
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Authors: | G Hallström B Lindeke A-H Khuthier MA Al-Iraqi |
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Institution: | 1. Department of Organic Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Box 574, S-751 23 Uppsala Sweden;2. Department of Chemistry, University of Mosul Iraq |
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Abstract: | Pargyline undergoes metabolic N-oxidation in rat and rabbit liver microsomal preparations. The reaction requires oxygen and is NADPH dependent. N-oxidation and N-demethylation are equal in both control and induced rat liver microsomes, while N-oxidation is more dominant in rabbit tissue. Experiments investigating the CO-sensitivity and the effects of metyrapone suggest that cytochrome P-450 systems are involved in both reactions in the rat while an additional enzyme is responsible for the N-oxidation in the rabbit. Pargyline N-oxide is characterized by chemical instability and undergoes two consecutive rearrangements to yield propenal and Schiff bases, the latter undergoing hydrolysis to aldehydes and primary amines. Accordingly, due to the inherent instability of the N-oxide, metabolic N-oxidation of pargyline is, in addition to α-carbon oxidation, indicated as a metabolic route to benzaldehyde. Similarly the ease with which pargyline N-oxide generates propenal implicates N-oxidation as a metabolic route to be considered when evaluating the toxicity of pargyline. |
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Keywords: | DI direct probe technique DNPH 2 4-dinitro-phenylhydrazine FID flame ionization detection GLC gas-liquid chromatography IR infrared MS mass spectrum NMR nuclear magnetic resonance TLC thin-layer chromatography |
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