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Purpose : The effect of pretreatment with amiloride (AML), an Na + / H + exchange inhibitor was studied in the middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia in rats. Materials and Methods : Male wistar rats were subjected to 2 hr of MCAO followed by 22-hr reperfusion. Grip strength, locomotor activity, and spontaneous alternation performance were assessed after 24 hr. Immediately after behavioral activities, animals were sacrificed and the oxidative stress markers were estimated in brains. Results : An elevation of thiobarbituric acid reactive substances (TBARS), reduction in glutathione, and antioxidant enzymes activities, namely glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) were observed following MCA occluded rats. Pretreatment with AML (0.91 and 1.82 mg/kg p.o) significantly reversed the MCAO-induced elevation in TBARS but could not reverse the other parameters. Paradoxically, AML further reduced the levels of GPx, GR, and SOD, but no significant changes were observed in the catalase activity, grip strength, and spontaneous alternation behavior of rats. Locomotor activity was reduced slightly but reversed on pretreatment with AML. Conclusions : Although pretreatment with single dose of AML showed reduction in oxidative stress markers, further multiple doses of AML as pre- and post-treatments are required to establish its potential to be used in cerebral ischemia.