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Development of the Nitrone-Based Spin Trap Agent NXY-059 to Treat Acute Ischemic Stroke

  1. Paul A. Lapchak1,2,3,*,
  2. Dalia M. Araujo2

Article first published online: 7 JUN 2006

DOI: 10.1111/j.1527-3458.2003.tb00252.x

Issue

CNS Drug Reviews

CNS Drug Reviews

Volume 9, Issue 3, pages 253–262, September 2003

Additional Information

How to Cite

Lapchak, P. A. and Araujo, D. M. (2003), Development of the Nitrone-Based Spin Trap Agent NXY-059 to Treat Acute Ischemic Stroke. CNS Drug Reviews, 9: 253–262. doi: 10.1111/j.1527-3458.2003.tb00252.x

Author Information

  1. 1

    Department of Neuroscience, University of California San Diego, La Jolla, CA;

  2. 2

    VASDHS, San Diego, CA, USA.

  3. 3

    Veterans Medical Research Foundation, San Diego, CA, USA.

*Address correspondence and reprint requests to: Paul A. Lapchak, Ph. D, Department of Neuroscience, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0624, USA. Tel.: +1 (858) 822–1297; Fax: +1 (858) 822–4106; E-mail: plapchak@ucsd.edu

Publication History

  1. Issue published online: 7 JUN 2006
  2. Article first published online: 7 JUN 2006

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Keywords:

  • Free radicals;
  • Hemorrhage;
  • Neuroprotection;
  • Nitrone;
  • Oxidative stress Spin trap

ABSTRACT

The only current FDA-approved treatment for acute ischemic stroke is thrombolysis with tissue plasminogen activator (tPA). However, there are numerous shortcomings to tPA treatment including an increased incidence of intracerebral hemorrhage (ICH) and a short therapeutic window (3–6 h). In recent years, studies have attempted to identify new therapeutics that might be neuroprotective following ischemic strokes. Free radical scavenging spin trap agents have been proposed as potential candidates for stroke therapy because of the hypothesized role of free radicals in the progression of stroke and ischemia-induced neurodegeneration. Novel spin trap agents like (disodium-[(tert-butylimino) methy1] benzene-1,3-disulfonate N-oxide (NXY-059) are of particular interest, not only because they are broad-spectrum nitrone-based free radical scavengers, but also because of their safety profile in humans. Moreover, the rationale for developing NXY-059 for the treatment of acute ischemic stroke is further supported by the drug's reported neuroprotective effects. In addition, NXY-059 may represent a useful adjunct stroke therapy to tPA, since preclinical studies have demonstrated that NXY-059 increases the therapeutic window for tPA and lowers the occurrence of tPA-induced ICH.

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