Relationship between the Neuroprotective Effect of Na^+/H^+ Exchanger Inhibitor SM-20220 and the Timing of Its Administration in a Transient Middle Cerebral Artery Occlusion Model of Rats

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The aim of this study was to determine the relationship between the neuroprotective effect of SM-20220(N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate)and the timing of its administration in an experimental stroke model. Two hours of occlusion followed by 22h of perfusion of the left middle cerebral artery(MCA)was performed by inserting a nylon thread into the MCA to occlude it, and pulling the thread to initiate reperfusion. Intravenous infusion of SM-20220 for 1h reduced the infarct volume at doses of 0.2-0.8mg/kg in a dose-dependent manner without causing changes in the systemic arterial blood pressure or blood gases, when SM-20220 administration was started 1 h after the onset of occlusion. Administration of SM-20220 at a dose of 0.4mg/kg also reduced the edema formation induced by ischemia. In contrast, SM-20220 failed to reduce the infarction, even at 1.6mg/kg, when administration was started 2h after the onset of occlusion. Thus, the therapeutic time window of SM-20220 for this transient MCA occlusion model is 1h. Daily administration of SM-20220(0.4mg/kg)for the 7d following 1.5h of middle cerebral artery occlusion reduced the infarct volume with statistical significance(p<0.05), showing that SM-20220 did not merely delay but prevented ischemic damage.
公益社団法人日本薬学会の論文
2001-07-01