Zeraati Fatemeh, Araghchian Malihe, Farjoo Mohammad Hadi
Department of Pharmacology, Hamedan University of Medical Sciences, Hamedan, Iran.
Anesth Pain Med. 2014 Jun 22;4(3):e19529. doi: 10.5812/aapm.19529. eCollection 2014 Aug.
Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects.
The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol.
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.
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.
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.
联合使用不同的镇痛药以提高药物疗效是一种推荐策略，旨在实现最佳治疗效果。
本研究旨在评估维生素C与两种镇痛药吗啡和曲马多之间相互作用的性质。
通过醋酸扭体试验评估雄性海军医学研究所（NMRI）小鼠的镇痛活性。每组使用四至六只动物获得结果。所有药物均腹腔注射。根据每种药物单独以及维生素C与曲马多或吗啡联合给药的剂量-反应曲线计算产生20%、50%和65%镇痛作用的有效剂量（ED）（ED20、ED50和ED65）。相互作用指数计算为实验ED/理论ED。对于每种药物组合，通过剂量-反应曲线的线性回归分析确定ED50、ED20和ED65，并使用t检验将它们与理论ED50、ED20和ED65进行比较。
所有药物的镇痛作用均呈剂量依赖性（维生素C的ED50为206.1mg/kg，曲马多为8.33mg/kg，吗啡为0.79mg/kg）。相互作用指数表明，维生素C与曲马多或吗啡联合给药在ED50和ED65时具有相加作用。然而，在ED20时，维生素C与曲马多或吗啡的组合显示出协同作用。组合的相互作用指数值表明维生素C/吗啡的效价比低于维生素C/曲马多。
本研究证明了维生素C与曲马多或吗啡之间相互作用的结果。结果表明，对镇痛的相互作用效应可能是协同的或相加的，这取决于效应水平。
