Gill R, Nordholm L, Lodge D
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Brain Res. 1992 May 15;580(1-2):35-43. doi: 10.1016/0006-8993(92)90924-x.
The neuroprotective effects of NBQX, a selective antagonist for the AMPA/kainate subtype of excitatory amino acid receptors, were investigated in a rat focal ischaemia model, involving permanent occlusion of the left middle cerebral artery (MCA). NBQX (3, 10 or 30 mg/kg) was administered i.v. immediately after MCA occlusion and again 1 h later. The highest dose of NBQX (2 x 30 mg/kg) gave significant protection against hemispheric (24%) and cortical (27%) ischaemic damage. The lower doses of NBQX (2 x 3 or 2 x 10 mg/kg) were ineffective. No protection was seen against caudate damage for any of the doses of NBQX tested. NBQX has a t1/2 of 30 min, therefore, a second experiment was done in which a dose of 30 mg/kg was given as an i.v. bolus followed immediately by an infusion of 10 mg/kg/h for 4 h, dosing was started immediately after MCA occlusion. This dosing regimen resulted in a mean plasma level over the 4 h of 17 micrograms/ml, and significant protection against the volume of hemispheric (29%) and cortical (35%) ischaemic damage, which was slightly better than that achieved with two bolus doses of 30 mg/kg. Once again no protection was seen against caudate damage. We conclude that NBQX, an AMPA/kainate antagonist was neuroprotective in a focal ischaemia model in the rat.
在大鼠局灶性缺血模型（涉及永久性阻断左大脑中动脉）中，研究了AMPA/海人酸亚型兴奋性氨基酸受体的选择性拮抗剂NBQX的神经保护作用。在大脑中动脉闭塞后立即静脉注射NBQX（3、10或30mg/kg），1小时后再次给药。最高剂量的NBQX（2×30mg/kg）对半球（24%）和皮质（27%）缺血损伤具有显著的保护作用。较低剂量的NBQX（2×3或2×10mg/kg）无效。在所测试的任何剂量的NBQX中，均未观察到对尾状核损伤的保护作用。NBQX的半衰期为30分钟，因此，进行了第二项实验，静脉推注30mg/kg剂量，随后立即以10mg/kg/h的速度输注4小时，在大脑中动脉闭塞后立即开始给药。这种给药方案导致4小时内的平均血浆水平为17μg/ml，并对半球（29%）和皮质（35%）缺血损伤的体积具有显著的保护作用，略优于两次推注30mg/kg所达到的效果。同样，未观察到对尾状核损伤的保护作用。我们得出结论，AMPA/海人酸拮抗剂NBQX在大鼠局灶性缺血模型中具有神经保护作用。
