Interaction between ethanol and opioids in a protozoan assay

Ethanol excess combined with opioids can be fatal due to their toxic interaction, yet the nature of the interaction is little documented. Since ethanol and some opioids have membrane stabilizing activity, the present study used a protozoan motility model to test the possibility that ethanol may interact with some opioids on this basis. The EC50 in motility reduction for ethanol, dextropropoxyphene, methadone and pethidine was 522.0 +/- 36.7 mM, 0.59 +/- 0.08 mM, 0.40 +/- 0.09 mM and 4.57 +/- 0.36 mM, respectively. When ethanol was combined with one of the three drugs in equitoxic doses at a ratio of 0.5:0.5, the predicted/observed EC50 values for ethanol-dextropropoxyphene, ethanol-methadone and ethanol-pethidine were 1.37, 1.11 and 1.00, each being close to unity, indicating an additive interaction. The interaction between ethanol and dextropropoxyphene was further explored at 0.25:0.75 and 0.75:0.25 equitoxic dose ratios, with the predicted/observed EC50 values of 0.98 and 0.97, also showing an additive interaction. This suggests that a non-specific interaction between ethanol and opioids may also take place in vivo, which could cause increased toxicity over and above the involvement of opioid receptors. Information from this study should aid understanding of the mechanism of interactions in human poisoning by agents with membrane stabilizing activity.