Evaluation of the effectes of Erythromycin and Dextromethorphan on morphine induced tolerance in mice

Abstract

Introduction:Several mechanisms (increasing NMDA receptors, increasing p-gp gene expression, etc.) are involved in the tolerance to the analgesic effects of morphine. Dextromethorphan is an antitussive and a p-gp substrate. On the other hand, erythromycin, is macrolide antibiotics, also has an inhibitory effect on p-gp.Aime: The aime of this study was to investigate the effects of dextromethorphan and erythromycin in the treatment of tolerance to the analgesic effects of morphine in mice.Matrial and Method:100 male mice in 10 groups of 10 in the weight range of 20-30 grams were randomly selected and given drug regimens of Saline (10 ml/kg, ip) or Morphine (25 mg/kg, ip) to develop tolerance to morphine once a day for fourteen days. Then on the fifteenth day, different doses of erythromycin (50, 100, 200 mg/kg, ip), or dextromethorphan (10, 20, 40 mg/kg, ip) and dextromethorphan (10 mg/kg, ip) + erythromycin (50 mg) /kg, ip) half an hour before the test injection of morphine (9 mg/kg, ip) was injected into the mice. Finally, the analgesic effects caused by the morphine (9 mg/kg, ip) were evaluated in the studied groups by the Hot plate method for one hour.Results & Conclusion: The results showed that different doses of dextromethorphan (10, 20, 40 mg/kg, ip) and erythromycin (50 mg/kg, ip) have a significant effect on returning tolerance to the analgesic effects caused by morphine.Also, in the combined injection of dextromethorphan (10 mg/kg, ip) + erythromycin (50 mg/kg, ip), a significant effect was observed in returning tolerance to analgesic effects.