Green A Richard, Lanbeck-Vallén Kerstin, Ashwood Tim, Lundquist Stefan, Lindström Böö Eva, Jonasson Hallgrimur, Campbell Mark
AstraZeneca R&D Charnwood, Bakewell Rd., Loughborough LE11 5RH, Sweden.
Brain Res. 2006 Feb 9;1072(1):224-6. doi: 10.1016/j.brainres.2005.12.035. Epub 2006 Jan 30.
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.
在永久性大脑中动脉闭塞（pMCAO）的大鼠中，研究了自由基捕获神经保护剂NXY - 059在大脑中的渗透情况。在右侧pMCAO或假手术15分钟后开始，以125mg/kg静脉推注，随后以125mg/kg/h的速度输注NXY - 059，持续4小时45分钟。5小时时，两组的血浆总NXY - 059浓度（微摩尔/升）相似[假手术组：623±44（6）；pMCAO组：605±43（5）]，右侧皮质中的药物浓度（纳摩尔/克）也相似[假手术组：6.92±1.05（6）；pMCAO组：6.14±2.18（6）]。随后在正常大鼠中进行的一项实验，以相似和更高的浓度（252mg/kg静脉推注和252mg/kg/h）输注NXY - 059，结果表明皮质中NXY - 059的浓度与血浆浓度呈线性增加。这些数据表明，NXY - 059确实能穿透对照动物的脑组织以及接受pMCAO的动物的缺血组织。
