Brain Penetration of the Novel Free Radical Trapping Neuroprotectant Nxy-059 in Rats Subjected to Permanent Focal Ischemia.
From: AstraZeneca R&D Charnwood, Bakewell Rd., Loughborough LE11 5RH, Sweden.
Brain research
- Publish Date: Feb 2006
- ISSN: 0006-8993
- Volume: 1072
- Issue: 1
- Pages: 224-6
- Medium: Print
- Language: English
- Citation (JAMA): Green A Richard, Lanbeck-Vallén Kerstin, Ashwood Tim, et al. Brain Penetration of the Novel Free Radical Trapping Neuroprotectant Nxy-059 in Rats Subjected to Permanent Focal Ischemia.. Brain Res. Feb 2006;1072:224-6
Abstract
The penetration of the free radical trapping neuroprotectant NXY-059 into the brain has been examined in rats subjected to permanent middle cerebral artery occlusion (pMCAO). NXY-059 (125 mg/kg bolus followed by 125 mg/kg/h) was infused for 4 h 45 min starting 15 min after right pMCAO or sham operation. At 5 h, there was a similar plasma total NXY-059 concentration (micromol/L) in both groups [sham: 623 +/- 44 (6); pMCAO: 605 +/- 43 (5)] and a similar drug concentration (nmol/g) in the right cortex [sham: 6.92 +/- 1.05 (6); pMCAO: 6.14 +/- 2.18 (6)]. A subsequent experiment in normal rats, infusing NXY-059 at both a similar and higher concentration (252 mg/kg bolus and 252 mg/kg/h), demonstrated that the concentration of NXY-059 in cortex increased linearly with respect to the plasma concentration. These data demonstrate that NXY-059 does penetrate brain tissue in control animals and ischemic tissue of animals subjected to pMCAO.
Mesh Headings (Keywords): Animals, Antioxidants, Benzenesulfonates, Brain Ischemia, Cerebral Cortex, Free Radicals, Infusions, Intravenous, Nitrogen Oxides, Rats
Check for Full Text / PubMed Unique Identifier (PMID): 16448628
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