Abstract
Currently, the only FDA-approved treatment for acute ischemic stroke (AIS) is the thrombolytic, tissue plasminogen activator (tPA; alteplase; activase). It has been proposed that both the spin trap agent NXY-059 (cerovive) and tenecteplase (TNK-tPA), which are currently in phase II clinical trials, may also be useful for the treatment of ischemic stroke. However, there is little information available concerning the dose-response profiles or therapeutic window for NXY-059 in a validated embolic stroke model, nor is there information available pertaining to the effects of combining NXY-059 with tenecteplase. Thus, we determined the pharmacological profile of NXY-059 on behavioral outcome following small clot embolic strokes in rabbits when administered alone or in combination with tenecteplase. Male New Zealand white rabbits were embolized by injecting a suspension of small blood clots into cerebral circulation via a carotid catheter. NXY-059 (0.1-100 mg/kg) was infused intravenously (IV), 1 h following embolization, whereas control rabbits received infusions of saline. We also determined the therapeutic window for NXY-059 by administering the drug 1, 3, or 6 h following embolic strokes. Lastly, in combination studies, NXY-059 wa...Continue Reading
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