Evaluation of the effects of Naproxen and Clarithromycin in morphine induced dependency in male mice

Abstract

Chronic use of opioid painkillers causes tolerance to the analgesic effect. One of the ability to increase tolerance is the increase of P-gp gene expression factors. Naproxen works by inhibiting both COX-1 and COX-2 enzymes. Clarithromycin is an antibiotic with a macrolide structure and induces the ability of P-gp. Objective: The objective of this study was to investigate chronic intraperitoneal injection of naproxen and clarithromycin on the occurrence of tolerance to the analgesic effect of morphine in male mice.Methods: 81 male mice in 9 groups of 9 in the weight range of 20-30 grams were randomly selected and received drug regimens containing naproxen and clarithromycin once a day for two weeks. Doses of naproxen (5, 10, 20 mg/kg, ip) and clarithromycin (2, 4, 8 mg/kg, ip) were injected every half hour before the daily injection of morphine. Then, on the 15th day, the anti-inflammatory substances caused by the morphine dose test (9mg/kg) were evaluated in different groups by the hot plate method. After conducting behavioral studies in different groups, the animals are anesthetized and blood is taken from the heart to measure the serum level of MDA and TAC.Results: The results indicated a significant effect in reducing tolerance in doses (20mg/kg) of naproxen and 8mg/kg) of clarithromycin.There were no significant changes in the serum levels of TCA and MDA in any of the groups compared to the control group.Conclusion: Taking high doses of naproxen and clariomycin are beneficial in reducing tolerance caused by morphine. We need more studies for human consumption with the aim of reducing tolerance.