title: 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.affiliation: AstraZeneca R&D Charnwood, Bakewell Rd., Loughborough LE11 5RH, Sweden.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Green
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lanbeck-Vallén
authors.forename: Tim
authors.initials: T
authors.lastname: Ashwood
authors.forename: Stefan
authors.initials: S
authors.lastname: Lundquist
authors.forename: Eva
authors.initials: E
authors.lastname: Lindström Böö
authors.forename: Hallgrimur
authors.initials: H
authors.lastname: Jonasson
authors.forename: Mark
authors.initials: M
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D007262:Infusions, Intravenous; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000975:Antioxidants; D001557:Benzenesulfonates; D005609:Free Radicals; D009589:Nitrogen Oxides; C120851:disufenton sodium