Abstract |
Recent results have demonstrated that the spin trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct volume in rats subjected to 2 hours of middle cerebral artery occlusion, even when given 1 to 3 hours after the start of recirculation. In the current study, the authors assessed the effect of NXY-059, a novel nitrone that is more soluble than PBN. Loading doses were given of 0.30, 3.0, or 30 mg x kg(-1) followed by 0.30, 3.0, or 30 mg x kg(-1) x h(-1) for 24 or 48 hours. Dose-response studies showed that when treatment was begun 1 hour after recirculation, 0.30 mg x kg(-1) had a small and 30 mg x kg(-1) a marked effect on infarct volume. At equimolar doses (3.0 mg x kg(-1) for NXY-059 and 1.4 mg x kg(-1) for PBN), NXY-059 was more efficacious than PBN. Similar results were obtained when a recovery period of 7 days was allowed. The window of therapeutic opportunity for NXY-059 was 3 to 6 hours after the start of recirculation. Studies of the transfer constant of [14C] NXY-059 showed that, in contrast to PBN, this more soluble nitrone penetrates the blood-brain barrier less extensively. This fact, and the pronounced antiischemic effect of NXY-059, suggest that the delayed events leading to infarction may be influenced by reactions occurring at the blood-endothelial interface.
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Authors | S Kuroda, R Tsuchidate, M L Smith, K R Maples, B K Siesjö |
Journal | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
(J Cereb Blood Flow Metab)
Vol. 19
Issue 7
Pg. 778-87
(Jul 1999)
ISSN: 0271-678X [Print] United States |
PMID | 10413033
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Benzenesulfonates
- Neuroprotective Agents
- Nitrogen Oxides
- nitrones
- disufenton sodium
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Topics |
- Animals
- Benzenesulfonates
- Blood-Brain Barrier
- Dose-Response Relationship, Drug
- Ischemic Attack, Transient
(drug therapy, pathology, physiopathology)
- Male
- Neuroprotective Agents
(administration & dosage, pharmacokinetics, therapeutic use)
- Nitrogen Oxides
(administration & dosage, pharmacology, therapeutic use)
- Rats
- Rats, Wistar
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