Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.
N P McGraw, N Castagnoli
Journal of Medicinal Chemistry March 1981 DOI: 10.1021/jm00135a012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacology study Peer reviewed |
|---|---|
| Population | Rabbit liver microsomes |
| Interventions | 1-(2 N-hydroxy metabolites |
| Key points | The authors suggest that N-oxidation of the pharmacologically active (R)-amine is inhibited by the S enantiomer, and that metabolic intermediate complex formation, favored by the (R)-amine, appears associated with loss of microsomal mixed-function N-oxidase activity. They predict that N-hydroxylation of pure (R)-amine may be a qualitatively more important pathway than with the racemic amine, even though this biotransformation may be 'suicidal.' |
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.