Otaplimastat (SP-8203) 是一种基质金属蛋白酶 (MMP) 抑制剂，以竞争方式阻断 NMDA 受体介导的兴奋性毒性。Otaplimastat 还具有抗氧化活性。Otaplimastat 可用于脑缺血损伤的研究。
Otaplimastat (SP-8203), a matrix metalloproteinase (MMP) inhibitor, blocks N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. Otaplimastat also exhibits anti-oxidant activity. Otaplimastat can be used for the research of brain ischemic injury[1][2][3].
Otaplimastat (87.5-350 μM; 20 min) protects neuronal cells against NMDA-induced cell death in a competitive manner[1].Otaplimastat (350 μM) inhibits Ca2+ influx following activation of NMDA receptors in primary cultured neuron[1].Otaplimastat (2-200 μM; pretreated for 4 h) significantly suppresses H2O2-induced cell death and reactive oxygen species production[2].
Otaplimastat (10-20 mg/kg; i.p. 30 min before occlusion and 1 h after reperfusion) prevents ischemic neuronal death in the occlusion model of MCA[1].Otaplimastat (5-10 mg/kg; i.p. daily for 10 days) attenuates impairment of stroke-induced motor function[2].
[1]. Noh SJ, et, al. SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor. Pharmacol Biochem Behav. 2011 Nov;100(1):73-80.
[2]. Noh SJ, et, al. SP-8203 reduces oxidative stress via SOD activity and behavioral deficit in cerebral ischemia. Pharmacol Biochem Behav. 2011 Mar;98(1):150-4.
[3]. Kim JS, et, al. Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study. Ann Neurol. 2020 Feb;87(2):233-245.
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