Coadministration of NXY-059 and tenecteplase six hours following embolic strokes in rabbits improves clinical rating scores

Experimental Neurology
Paul A LapchakJustin A Zivin

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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Citations

May 23, 2007·American Journal of Therapeutics·Justin A Sattin, Justin A Zivin
Oct 19, 2012·Science Translational Medicine·Patrick Lyden, Paul Lapchak
Oct 12, 2010·Stroke; a Journal of Cerebral Circulation·Xiang FanXiaoying Wang
Mar 16, 2007·Expert Opinion on Emerging Drugs·Paul A Lapchak, Dalia M Araujo
Apr 26, 2006·Expert Opinion on Pharmacotherapy·Sheila A Doggrell
Jul 12, 2008·Expert Opinion on Investigational Drugs·Paul A Lapchak
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Jul 13, 2004·Experimental Neurology·Kenneth R Wagner, Edward C Jauch
Mar 2, 2006·The Annals of Pharmacotherapy·Jeffrey J Fong, Denise H Rhoney
Jul 19, 2008·Stroke; a Journal of Cerebral Circulation·Malcolm R MacleodGeoffrey A Donnan
Dec 1, 2007·Stroke; a Journal of Cerebral Circulation·Geoffrey A Donnan
Sep 2, 2006·Stroke; a Journal of Cerebral Circulation·David C Hess
Dec 17, 2008·Stroke; a Journal of Cerebral Circulation·Maria PhilipSean I Savitz
Apr 1, 2021·Cellular and Molecular Neurobiology·Devendra SinghK H Reeta
Sep 22, 2018·Pharmacology & Therapeutics·Thavarak OukSophie Gautier

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