Entrance into brain of dextropropoxyphene and the toxic metabolite norpropoxyphene.

Several studies show that dextropropoxyphene after oral administration is intensively biotransformed to norpropoxyphene by first pass metabolism in the liver. While dextropropoxyphene is analgesic, cardiotoxic and shows CNS toxicity with convulsions and respiratory depression, norpropoxyphene is cardiotoxic to the same degree as dextropropoxyphene, but is without analgesic or CNS-toxic effects (Lund-Jacobsen, 1978). This principal difference between the effects of dextropropoxyphene and norpropoxyphene might be due to differences in penetration into the brain. We investigated the penetration of the two compounds in 14C-labelled moities into the brain of rats by the technique originally described by Oldendorf (1970). By this method the extraction of dextropropoxyphene was found extremely high, while it was much lower for the metabolite. The extraction percentage for dextropropoxyphene after 5 and 10 S was 350 +/- 34.1 and 164 +/- 15.2, respectively, while the values for norpropoxyphene was 62 +/- 6.2 and 44 +/- 4.1 (mean +/- S.E.M.), respectively. This difference may at least partly explain the missing CNS-symptoms with the metabolite.