Otaplimastat (SP-8203) is a MMP Inhibitor

Oxidative stress is a major cause of neuronal cell death, including ischemic brain injury. Cell culture models and animal experiments indicated neuronal cell death can produce reactive oxygen species such as O2− (superoxide anion), <sup>·</sup>OH (hydroxyl radical), H2O2 (hydrogen peroxide). They attack lipids, proteins, and DNA of neurons in ischemia brain tissues. The neuronal cell membrane and the mitochondrial membrane constitute high levels of polyunsaturated fatty acids which can be easily attacked by the ROS. Ultimately, they play a pivotal role in brain injury. Otaplimastat reduces oxidative stress via SOD activity and behavioral deficit in cerebral ischemia. In addition, Otaplimastat shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor. In a word, Otaplimastat can be used for the research of brain ischemic injury.

Otaplimastat protects neuronal cells against NMDA-induced cell death in a competitive manner. It inhibits Ca<sup>2+</sup> influx following activation of NMDA receptors in primary cultured neuron. Otaplimastat significantly suppresses H2O2-induced cell death and reactive oxygen species production. Otaplimastat (5 and 10 mg/kg; i.p.; rats; daily for 10 days) remarkably reduces brain infarct volume and lipid peroxidation products in the MCA-occluded rats but MK-801 didn’t. Moreover, Otaplimastat significantly improved neurological deficits such as shortening of latency time in Rota rod performance. Otaplimastat may be more effective for multiple-target mechanisms of ischemic stroke. In addition, Otaplimastat significantly improves spatial learning and memory in the water maze test.

In summary, Otaplimastat blocks NMDA receptor-mediated excitotoxicity in a competitive manner. Otaplimastat also exhibits antioxidant activity. It can be used for the research of brain ischemic injury.


Noh SJ, et, al. Pharmacol Biochem Behav. 2011 Nov;100(1):73-80.; Noh SJ, et, al. Pharmacol Biochem Behav. 2011 Mar;98(1):150-4.