Ethanol does not increase lethality due to propoxyphene in rats.

Male Wistar rats (210-330 g) were used as test animals. Propoxyphene (175 mg/kg) and ethanol (2 g/kg) were administered by gastric intubation, naloxone (2 mg/kg) by subcutaneous injection. Four groups, each consisting of 19 rats received either of the following drug treatments: Propoxyphene; ethanol + propoxyphene; naloxone + propoxyphene; and naloxone + ethanol + propoxyphene. The drugs were given in the sequence mentioned at the beginning of the experiment. Naloxone was also given 45 and 90 min later. Mortality was reduced to 42% in the group that received ethanol and propoxyphene as compared to 73% in the group that received propoxyphene only. Naloxone protected against lethality in both groups. A rise in the propoxyphene/norpropoxyphene (P/N) ratio due to an increase in the absolute concentrations of propoxyphene and a decrease in the absolute levels of norpropoxyphene in blood, brain and heart tissues was observed in the ethanol + propoxyphene group, compared to the propoxyphene group. Although these pharmacokinetic data indicate impaired propoxyphene metabolism in the presence of ethanol, ethanol did not enhance propoxyphene induced lethality. This is also contrary to suggestions from previous studies. Our results demonstrate that at least in one species and at one dose ratio (ethanol/propoxyphene) ethanol might reduce the lethality caused by propoxyphene alone. This suggests antagonism between the two drugs, probably in the central nervous system.