Studies on chiral interactions of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane and the corresponding N-hydroxy metabolites with cytochrome P-450.
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.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000378:metabolism*; D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011619:Psychotropic Drugs / Q000378:metabolism*; D011817:Rabbits; D013237:Stereoisomerism
D000662:Amphetamines; D011619:Psychotropic Drugs; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D003577:Cytochrome P-450 Enzyme System