Brain penetration of the novel free radical trapping neuroprotectant NXY-059 in rats subjected to permanent focal ischemia.

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.

• Authors: A Richard Green, Kerstin Lanbeck-Vallén, Tim Ashwood, Stefan Lundquist, Eva Lindström Böö, Hallgrimur Jonasson, Mark Campbell
• Journal: Brain research (Brain Res) Vol. 1072 Issue 1 Pg. 224-6 (Feb 09 2006) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16448628 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Benzenesulfonates
• Free Radicals
• Nitrogen Oxides
• disufenton sodium

Topics

• Animals
• Antioxidants (administration & dosage, pharmacokinetics, therapeutic use)
• Benzenesulfonates (administration & dosage, pharmacokinetics, therapeutic use)
• Brain Ischemia (metabolism)
• Cerebral Cortex (metabolism)
• Free Radicals (metabolism)
• Infusions, Intravenous
• Nitrogen Oxides (administration & dosage, pharmacokinetics, therapeutic use)
• Rats