(-)-Dizocilpine maleate ((-)-MK 801 (Maleate)) is a potent, selective and non-competitive NMDA receptor antagonist with Kd of 37.2 nM in rat brain membranes.

NMEA:Kd：37.2nM

在体外神经生理学研究中，使用大鼠皮层切片进行的试验表明，dizocilpine对N-Me-D-Asp引起的去极化反应显示出强大、选择性且非竞争性的拮抗作用，但对kainate或quisqualate无效。phencyclidine、ketamine、SKF 10047及dizocilpine的对映体作为N-Me-D-Asp拮抗剂的效力与它们作为[3H]dizocilpine结合抑制剂的效力密切相关（r = 0.99）。这暗示dizocilpine的结合位点与N-Me-D-Asp受体相关联，并为dizocilpine作为抗惊厥化合物的作用机制提供了解释。

所有对照组大鼠在缺血性脊髓损伤(ISCI)后呈现严重的永久性神经功能缺陷，而经dizocilpine处理的大鼠在神经功能结果上具有统计学意义上的改善(P < .05)并显示良好恢复。组织病理学揭示，对照组大鼠腰段灰质中出现严重的神经元坏死，而dizocilpine处理的大鼠则显示轻微损伤。这些结果证明，ISCI前给予单剂量dizocilpine可以提供显著的神经保护作用。

In vitro binding assays:For in vitro binding assays, cerebral cortices from male Sprague-Dawley rats (200-300 g) are homogenized in 9 volumes of ice-cold sucrose by nine strokes with a Teflon/glass homogenizer at 500 rpm. The homogenate is centrifuged for 10 min at 1000 x g, and the supernatant is recentrifuged at 10,000 x g for 20 min at 4 ℃. The pellet is suspended in assay buffer and incubated for 20 min prior to final centrifugation at 10,000 x g for 20 min at 4 ℃. The pellet is resuspended in assay buffer (70 ml per gram of original tissue). Binding of [3H] dizocilpine is measured by incubating 750 ul duplicate aliquots of this crude membrane suspension (=0.75 mg of protein) with 100 ul of buffer containing displacer or of buffer alone (total binding), 100 ul of 50 nM [3H] dizocilpine, and 50 ul of buffer for 60 min at 23 ℃. Nonspecific binding is defined by unlabeled dizocilpine. Incubation is terminated by rapid filtration through Whatman GF/B filters, which are washed immediately with two 5-ml portions of ice-cold assay buffer in a Brandel M 24-R cell harvester. The time required for the complete filtration and washing procedure is less than 10 sec. Radioactivity on the filters is determined by liquid scintillation counting in standard vials with 10 ml of Hydrofluor at 41% counting efficiency.

Cell lines: mixed neuronal/glial cell culturesConcentrations: 10 μMIncubation Time: 30 minutesMethod: Primary mixed neuronal/glial cultures are prepared from fetal rat brains. Mature cultures are exposed to dissolved isoflurane [0.4 mM (1.8 minimum alveolar concentration) or 1.6 mM (7 minimum alveolar concentration)] or dizocilpine (10 μM), and NMDA (0 or 3 μM) at 37 ℃ for 30 minutes. Apoptosis is assessed using terminal-deoxy-nucleotidyl end-nick labeling oligonucleosomal DNA fragmentation enzyme-linked immunosorbent assay, and caspases-3 and -9 activation assays.

Animal Models: ischemic spinal cord injury medelFormulation: N/ADosages: 1 mg/kgAdministration: IV