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.