Effects of sympathomimetic agents on opiate analgesia, tolerance and dependence in mice

The effects of chronic pretreatment with ephedrine and phenylpropanolamine (PPA) on the antinociceptive activities of morphine and codeine, as well as their effects on the induction and expression of tolerance to, and dependence on morphine and codeine in mice are reported. Chronic pretreatment with ephedrine or PPA attenuated the antinociceptive effects of subsequently administered morphine or codeine. When administered during the induction phase, sympathomimetics enhanced opiate tolerance with little or no effect on the development of physical dependence. Given in the expression phase, ephedrine and PPA did not significantly affect tolerance, whereas there was significant suppression of withdrawal signs. The possible implications of these results are discussed.