Research and Development of the Free Radical Scavenger Edaravone as a Neuroprotectant

作者：Toshiaki Watanabe, Masahiko Tanaka, Kazutoshi Watanabe, Yasuo Takamatsu, Akihiro Tobe · 发表于：YAKUGAKU ZASSHI · 年份：2004 · DOI：10.1248/yakushi.124.99 · 被引用次数：111 · 研究领域：Biochemical effects in animals、Coenzyme Q10 studies and effects、Free Radicals and Antioxidants

Increasing data suggest that oxygen free radical species play detrimental roles in ischemic diseases. A free radical scavenger capable of inhibiting oxidative injury is expected to become a new drug for the treatment of ischemic diseases such as cerebral ischemia. Edaravon (3-methyl-1-phenyl-2-pyrazolin-5-one), which has been developed as an neuroprotective agent for more than 15 years since its discovery, is approved for the treatment of acute cerebral infarction. In this paper, the pharmacologic characteristics and clinical effects of edaravone are reviewed. In early stage of investigation, edaravone was found to have promising activities as an antioxidative radical scavenger, quenching hydroxyl radical (.OH) and inhibiting both .OH-dependent and .OH-independent lipid peroxidation. Edaravone showed inhibitory effects on both water-soluble and lipid-soluble peroxyl radical-induced peroxidation systems, which are different from the inhibitory effects of vitamins C and E in each system, respectively. Oxidative injury to cultured endothelial cells caused by arachidonate (AA) peroxides is prevented in the existence of edaravone. To clarify the characteristics of this free radical scavenger, further investigation was carried out. Edaravone ameliorated exacerbation of cortical edema induced by a focal ischemia-reperfusion model in rats, suggesting inhibitory effects on oxidative injury to the blood-brain barrier (BBB). Additionally, edaravone also prevented rat cortical edema caus...