Morphine metabolism and normorphine in Papaver somniferum

Abstract

Normorphine has been established as an active metabolite of morphine in P. somniferum. This was done by, (a) demonstrating the presence of normorphine throughout the life cycle of the plant, (b) finding normorphine- 14C after feeding morphine- 14C via the roots, and (c) exposing opium poppies to 14CO 2 under steady state conditions which led to morphine and normorphine of the same specific activity. Feeding normorphine- 14C showed that the N-demethylation step is irreversible. A sensitive procedure was developed for the detection of normorphine in the presence of large amounts of morphine; using this procedure, normorphine was found in raw opium. These results indicate that the major, if not the sole, morphine degradative pathway involves an initial demethylation to normorphine, which is subsequently degraded to non-alkaloidal metabolites. The high rates of turnover observed led to the conclusion that the morphine alkaloids do play an active metabolic role, perhaps as specific methylating agents.