title: Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models.
abstract: Free radical-mediated neuronal cell damage is an important pathological process in ischemic stroke. We have previously reported a novel dual-functional agent, 2-[[(1,1-dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a derivative of tetramethylpyrazine armed with anitrone moiety. In this report, we further evaluate TBN'stherapeutic parameters in a rat middle cerebral artery occlusion (MCAO) model. Its abilities to cross the blood-brain barrier, scavenge free radicals, and inhibit Ca(2+) influx were also investigated. TBN showed significant activity in both the transient MCAO (t-MCAO) and permanent MCAO (p-MCAO) stroke models in the rat. The therapeutic time window is 8 hr in the t-MCAO model. TBN readily crossed the blood-brain barrier and in vitro had strong activity in neutralizing ·OH, O(-)(2)·, and ONOO(-) and significantly decreased intracellular Ca(2+) concentration. TBN is a promising new treatment forischemic stroke, with multiple mechanisms of action. It blocks Ca(2+) overload and neutralizes ·OH, O(-)(2)·, and ONOO(-).
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Sun
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Gaoxiao
authors.initials: G
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhong
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Zhai
authors.forename: Linda
authors.initials: L
authors.lastname: Wang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011719:Pyrazines; C017953:tetramethylpyrazine