Our interest in structure-metabolism relationships of pharmacologically active l-phenyl-2-aminopropanes has led to in vivo investigations of the fate of the psychotomimetic amine l-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1). Compound 1 was resolved via its o-nitrotartranilate salts and the absolute configurations were found to be (S)-( + ) and (fi)-(-). Determination of the enantiomeric composition of unmetabolized amine excreted in the urine of rabbits treated with racemic 1 established the R/S ratio to be equal to or greater than 1. With the aid of 1-14C (labeled at the benzylic position) ft has been established that 1 was extensively metabolized by the rabbit and that of several suspected metabolites only l-(2,5-dimethoxy-4-carboxyphenyl)-2-aminopropane was excreted to any great extent.

Halomon is metabolized by mouse and human hepatic cytochrome P-450 enzymes, the identities of which remain unknown. Hepatic metabolism of halomon is very consistent with the concentrations of halomon measured in mouse tissues and urine after i.v. administration of the drug.