Ephedrine and Phenylpropanolamine Potentiate the Lethal Toxicity of Morphine and Codeine in Naive Mice

Kelvin Chan, University of Wolverhampton, United Kingdom

Abstract

The effects of ephedrine and phenylpropanolamine, (PPA) on the acute lethal toxicity of morphine and codeine in naive mice are reported. Moderate doses (20, 40, 80 mg kg-1, i.p.) of ephedrine or PPA led to no mortality on their own. Morphine had an LD50 of 267.8 (262.5-272.I) mg kg-1 after subcutaneous (s.c.) administration. On pretreatment with ephedrine, the LD50 of morphine decreased approximately 5-fold; while it decreased by between 3 to 5 times on pretreatment with PPA. The lethal toxicity of codeine was similarly enhanced by pretreatment with these sympathomimetics, in a clearly dose-dependent manner. The data suggest that these sympathomimetics enhance opioid toxicity. The possible clinical implications of these findings are discussed.