Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, Mexico; Centro de Investigación para el Desarrollo Industrial, Universidad Autónoma de Guadalajara, Jalisco, Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, Mexico.
Eur J Pharmacol. 2017 Jun 15;805:51-57. doi: 10.1016/j.ejphar.2017.03.021. Epub 2017 Mar 14.
The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED =0.94±0.2mg/kg), naproxen (ED=3.18±0.4mg/kg), and ketorolac (ED=16.4±1.9mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED=0.39±0.06mg/kg, p.o.), naproxen (ED=33.9±3.9mg/kg, p.o.) or ketorolac (ED=6.49±1mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain.
本研究旨在探讨 α2-肾上腺素受体激动剂替扎尼定是否能增强萘普生和酮咯酸的抗炎和镇痛作用，同时降低胃损伤和自发性活动的发生率。在角叉菜胶试验中检测抗炎作用，替扎尼定（ED=0.94±0.2mg/kg）、萘普生（ED=3.18±0.4mg/kg）和酮咯酸（ED=16.4±1.9mg/kg）的口服给药呈剂量依赖性抗炎作用。在福尔马林试验中检测镇痛作用，替扎尼定（ED=0.39±0.06mg/kg，po）、萘普生（ED=33.9±3.9mg/kg，po）或酮咯酸（ED=6.49±1mg/kg，po）的给药均呈剂量依赖性镇痛作用。考虑到替扎尼定/萘普生和替扎尼定/酮咯酸的 ED 值为 1:1，确定了这两种药物联合应用的效果。此外，替扎尼定/萘普生和替扎尼定/酮咯酸联合应用具有抗炎和镇痛作用。替扎尼定/酮咯酸联合应用比替扎尼定/萘普生联合应用更有效，在炎症（相互作用指数=0.03 替扎尼定/酮咯酸和 0.07 替扎尼定/萘普生）和疼痛（相互作用指数=0.005 替扎尼定/酮咯酸和 0.01 替扎尼定/萘普生）过程中均如此。在这两种情况下，替扎尼定都将萘普生和酮咯酸的胃肠道耐受性提高了 50%。此外，与单独使用替扎尼定相比，替扎尼定与萘普生或酮咯酸联合使用不会以相同的方式改变自发性活动。鉴于替扎尼定能增强萘普生或酮咯酸的抗炎和镇痛作用，同时提高胃耐受性，替扎尼定可能在炎症和疼痛的临床治疗中具有治疗优势。
