Ascorbic Acid Interaction With Analgesic Effect of Morphine and Tramadol in Mice

BACKGROUND Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects. OBJECTIVES The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol. MATERIALS AND METHODS The analgesic activity was assessed by the acetic acid writhing test in male Naval Medical Research Institute (NMRI) mice. The results were obtained using four to six animals in each group. All the drugs were injected intraperitoneally. The effective doses (ED) that produced 20%, 50%, and 65% antinociception (ED20, ED50 and ED65) were calculated from the dose-response curve of each drug alone as well as co-administration of ascorbic acid and tramadol or morphine. The interaction index was calculated as experimental ED/theoretical ED. For each drug combination, ED50, ED20 and ED65 were determined by linear regression analysis of the dose-response curve, and they were compared to theoretical ED50, ED20 and ED65 using t-test. RESULTS The antinociceptive effects of all drugs were dose-dependent (ED50was 206.1 mg/kg for ascorbic acid, 8.33 mg/kg for tramadol, and 0.79 mg/kg for morphine). The interaction index demonstrated additive effects at ED50 and ED65 for co-administration of ascorbic acid and tramadol or morphine. However, at ED20, combination of ascorbic acid and tramadol or morphine showed synergic effects. The interaction index values of the combinations demonstrated the potency ratio of ascorbic acid/morphine to be lower than ascorbic acid/tramadol. CONCLUSIONS This study demonstrated the results of interactions between ascorbic acid and tramadol or morphine. The results showed that the interaction effects on antinociception may be synergistic or additive, depending on the level of effect.