脳保護剤(フリーラジカル消去剤)エダラボンの研究開発

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概要

• 論文の詳細を見る

• 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-l-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 caused by intracortical AA infusion in which free radical production and subsequent oxidative injury to the BBB are involved. With advances in in vivo measurement technology of oxygen radicals, edaravone was shown to inhibit postischemic increases in ・ OH production and tissue injury in the penumbral or recirculated area in rat cerebral ischemia models. In clinical studies, edaravone improved the core neurologic deficits, activities of daily living, and functional outcome of stroke patients. Furthermore, a study using proton magnetic resonance spectroscopic techniques showed that edaravone preserved 7V-acetyl-aspartate in stroke patients, a promising neuronal marker in the brain. Further investigation is essential for a better understanding of free radical-mediated cerebral injury during ischemia followed by recirculation. We hope that edaravone represents a promising neuroprotectant for drug therapy in acute cerebral ischemia.

• 公益社団法人日本薬学会の論文
• 2004-03-01

著者

• 田中 正彦

  三菱ウェルファーマ株式会社創薬本部開発部門

• 渡辺 俊明

  三菱ウェルファーマ株式会社営業本部医薬マーケティング部門

• 渡邉 和俊

  三菱ウェルファーマ株式会社創薬本部創薬第1研究所

• 高松 康雄

  三菱ウェルファーマ株式会社創薬本部研究部門

• 戸部 昭広

  三菱ウェルファーマ株式会社戦略本部

• 田中 正彦

  三菱ウェルファーマ株式会社 開発本部開発推進部 開発企画グループ

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