BIOTRANSFORMATION OF AN ANTIHYPERTENSIVE ARYLALKYLAMINE ANALOG IN THERAT

1. The excretion and metabolism of thyl]-5-methoxy-N,alpha-dimethyl-2- (phenylethynyl) benzenepropanamine (RWJ-26240) in the Wistar rat has b een investigated after a single oral dose of C-14-RWJ-26240 (50 mg/kg free base). 2. Plasma samples were obtained for 24 h after dosing and urine and faecal samples were collected over 8 days, and they accounte d for 0.9 and 96 % of the dose, respectively. 3. Representative sample s of plasma, urine and faecal samples were purified for metabolite iso lation and identification using HPLC, tie, mass spectra (CI and EI), H -1-NMR and derivatization. 4. Unchanged RWJ-26240 plus 11 metabolites were identified and accounted for > 80 % of the sample radioactivity. 5. Four metabolic pathways for RWJ-26240 are proposed; namely (1) N-de methylation, (2) O-demethylation, (3) phenyl hydroxylation and (4) N-d ealkylation. Pathways 1-3 appeared to be quantitatively more important .