Department of Pharmacology, Sree Siddaganga College of Pharmacy, Tumkur, Karnataka, India.
Toxicol Mech Methods. 2012 Nov;22(9):674-8. doi: 10.3109/15376516.2012.716092.
N-methyl-D-aspartate (NMDA) antagonists and γ-aminobutyric acid (GABA) agonists are proven protective in various animal models of ischemic brain damage. Tramadol, a centrally acting opioid analgesic reportedly possesses NMDA antagonistic and GABA agonistic properties, with additional ion channel blocking activity. The aim of the present study was to evaluate the possible neuroprotective effect of tramadol hydrochloride in a rat model of transient forebrain ischemia. Male Wistar rats were pretreated with tramadol hydrochloride at doses of 10 and 20 mg/kg b.w. intraperitoneally for 4 days and were subjected to 30 min occlusion of bilateral common carotid arteries followed by reperfusion for 24 h. Impairment in sensorimotor functions was evaluated by beam walking task, spontaneous locomotor activity and hanging wire test. Animals were sacrificed and the brain homogenates were used for estimating the levels of lipid peroxidation, a marker for extent of oxidative stress. Ischemic rats exhibited a significant decrease in locomotion, grip strength and increase in beam walking latency. Tramadol attenuated the post ischemic motor impairment evidenced by improvement in the performance in sensorimotor tests. The extent of lipid peroxidation was significantly (p < 0.001) reduced by tramadol pretreatment which was higher in ischemic control. This study demonstrates the neuroprotective effect of tramadol against transient forebrain ischemia in rats.
N-甲基-D-天冬氨酸（NMDA）拮抗剂和γ-氨基丁酸（GABA）激动剂已被证明在各种缺血性脑损伤动物模型中具有保护作用。曲马多是一种中枢作用的阿片类镇痛药，据报道具有 NMDA 拮抗和 GABA 激动作用，并有额外的离子通道阻断活性。本研究旨在评估盐酸曲马多在大鼠短暂性前脑缺血模型中的可能神经保护作用。雄性 Wistar 大鼠预先用盐酸曲马多以 10 和 20mg/kg 体重的剂量腹膜内给药 4 天，并进行 30 分钟双侧颈总动脉闭塞，然后再进行 24 小时再灌注。通过行走棒试验、自发运动活性和悬线试验评估感觉运动功能障碍。动物被处死，脑匀浆用于估计脂质过氧化水平，这是氧化应激程度的标志物。缺血大鼠的运动、握力明显下降，行走棒潜伏期明显延长。曲马多预处理减轻了缺血后运动障碍，表现为感觉运动测试的表现改善。曲马多预处理显著降低（p<0.001）脂质过氧化程度，缺血对照组的程度更高。本研究表明曲马多对大鼠短暂性前脑缺血具有神经保护作用。
