title: BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and attenuates cerebral ischemic injury in stroke.
abstract: Stroke is one of the three diseases that cause human death in current world, and it is the common, frequently occurring disease in the middle-old ages. NMDA receptors mediate glutamate-induced cell death when intensely or chronically activated, which is an important cause of neuronal cell death after acute injuries. Here, we demonstrated that BQ-869, a potent NMDA receptor antagonist, blocked NMDA receptor in concentration-dependent and dose-dependent manner, attenuated NMDA-induced Ca(2+) influx, inhabited NMDAR-mEPSC in hippocampal pyramidal neurons, improved athletic ability of rats with MACO, decreased infarction size in focal cerebral ischemia rats and reduced stroke mortality. Taken together, our data demonstrate the neuroprotective effect of BQ-869 might be through inhibiting NMDA-mediated excitotoxicity. These findings indicate that BQ-869 is the most potent antagonist of NMDA receptors, and provide new insights with potential therapeutic applications for the treatment of stroke.
authors.affiliation: Department of Neurosurgery, Jinshan Hospital, Fudan University Shanghai 201500, People's Republic of China.
authors.forename: Guo
authors.initials: G
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for Anti-tumor Protein Therapeutics, Qinghua University Beijing 100000, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinshan Hospital, Fudan University Shanghai 201500, People's Republic of China.
authors.forename: Er-Song
authors.initials: ES
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy*
chemical_list: C000605322:BQ-869; D018691:Excitatory Amino Acid Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate
keywords: BQ-869; MACO; NMDA receptor; cerebral ischaemia; excitotoxicity