BIOTRANSFORMATION OF THE ANTIDEPRESSANT DL-ROLIPRAM .1. ISOLATION ANDIDENTIFICATION OF METABOLITES FROM RAT, MONKEY, AND HUMAN URINE

The metabolic pathway of DL-rolipram was studied in two animal species and in man. Metabolites were isolated from rat, rhesus monkey, and fr om human urine by preparative HPLC and identified by MS and NMR analys is. In total, the structures of 7 degradation products could be elucid ated. Rolipram was metabolized by ether cleavage at the methoxy and cy clopentyloxy groups and by hydroxylation in positions 2 or 3 of the cy clopentyloxy ring followed by sulphation. Additionally, but exclusivel y in man, the 5-position of the pyrrolidone ring was hydroxylated.