Peripheral antinociceptive effects of N-methyl morphine.

Morphine and N-methyl morphine were compared in two antinociceptive tests in mice, the hotplate and acetic acid-induced writhing. Whereas morphine was active in both models, N-methyl morphine was only active in the writhing model. In this model, the antinociceptive effects of N-methyl morphine were antagonized by both naloxone and N-methyl nalorphine. In separate experiments the two quaternary analogues were both [14C]-labelled and shown not to penetrate the blood brain barrier. These results indicate a peripheral site of action for the opioid antinociceptive effects of N-methyl morphine in the writhing model.