NXY-059, a free radical--trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species

Stroke. 2001 Jan;32(1):190-8. doi: 10.1161/01.str.32.1.190.

Abstract

Background and purpose: NXY-059 is a novel nitrone with free radical-trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke.

Methods: Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify motor and spatial deficits. Five minutes after permanent occlusion of the right middle cerebral artery, monkeys received a 1-mL intravenous infusion of either saline or NXY-059 (28 mg x kg(-1)), and osmotic minipumps, model 2001D, were implanted subcutaneously to provide continuous drug or saline infusion for 48 hours. Drug-filled pumps released NXY-059 at 16 mg x kg(-1) x h(-1). The monkeys were retested 3 and 10 weeks after surgery to assess functional disability. Surgery, behavioral testing, and histology were all done blinded to treatment condition.

Results: NXY-059-treated monkeys were significantly better at reaching with their hemiparetic arm than were saline-treated monkeys when retested 3 weeks (P:<0.01) and 10 weeks (P:<0.01) after surgery. Drug treatment also significantly lessened the degree of spatial perceptual neglect (P:<0.01), a debilitating though ameliorating consequence of this infarct. NXY-059 treatment reduced the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter.

Conclusions: This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. These findings provide considerable encouragement for the clinical development of NXY-059.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Arm / physiopathology
  • Behavior, Animal / drug effects
  • Benzenesulfonates
  • Body Temperature / drug effects
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / physiopathology
  • Callithrix
  • Choice Behavior / drug effects
  • Disease Models, Animal
  • Free Radical Scavengers / administration & dosage*
  • Hemodynamics / drug effects
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology
  • Infusions, Intravenous
  • Kinesis / drug effects
  • Motor Activity / drug effects
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacokinetics
  • Nitrogen Oxides / administration & dosage*
  • Nitrogen Oxides / blood
  • Paresis / drug therapy
  • Paresis / etiology
  • Paresis / physiopathology
  • Perceptual Disorders / drug therapy
  • Perceptual Disorders / etiology
  • Perceptual Disorders / physiopathology

Substances

  • Benzenesulfonates
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Nitrogen Oxides
  • disufenton sodium