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.
- Lethal Toxicity,
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