Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.

doi:10.1021/JM00135A012

Paper

Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.

Published Mar 1, 1981 · N. Mcgraw, N. Castagnoli

Journal of medicinal chemistry

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Abstract

The stereoselective pharmacological behavior and metabolism of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane have led to an investigation of the interactions of the racemic amine, its enantiomers, and the corresponding N-hydroxy metabolites with rabbit liver microsomal cytochrome P-450. An examination of the formation of cytochrome P-450 metabolic intermediate complexes with these species suggests that N-oxidation of the pharmacologically active (R)-amine in inhibited by the S enantiomer. Additionally, metabolic intermediate complex formation [favored by the (R)-amine] appears to be associated with loss of microsomal mixed function N-oxidase activity. The results have led to the prediction that N-hydroxylation of pure (R)-amine may be a qualitatively more important pathway than that observed with racemic amine even though this biotransformation may be suicidal.

In Vitro Study

Study Snapshot

N-hydroxylation of the psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane may be a more important pathway than racemic amine, even if it is suicidal.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.

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References

Citations

Synthesis and anti-cancer activity of 2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides.

2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides show anti-cancer activity against various human cancer cell lines, with dimethylamino-methyl analogs being more active.

Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. XII. Enantioselectivity and temperature dependence in microsomes and reconstituted cytochrome P-450 systems from rat liver.

Different modes of interaction with the active site of P-450 contribute to the different behavior of substrates in the metabolism of phenylalkylamines.

Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. IX. A comparative study with enantiomeric 2-nitroso-1-phenylpropane in microsomes and a reconstituted cytochrome P-450 system from rat liver.

Enantiomeric C-nitroso compounds show different kinetics of complex formation, while N-hydroxyamphetamine enantiomers show high and equal rates of complex formation.