Edaravone (formerly known as Radicut; MCI-186; NCI-C03952; NSC 12; Norantipyrine; Norphenazone; trade name: Radicava) is a novel and potent free radical scavenger that has been used clinically to reduce the neuronal damage following ischemic stroke. In May 2017, Edaravone was approved by FDA to treat patients with amyotrophic lateral sclerosis (ALS). Edaravone inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. It was approved by FDA in May 5th 2017 for the treatment of amyotrophic lateral sclerosis (ALS). Edaravone reduces apoptosis and necrosis caused by glutamate. Pretreatment of edaravone (500 μM) reverses these changes to approximately normal levels.
理化性质和储存条件
| Molecular Weight (MW) | 174.2 |
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| Formula | C10H10N2O |
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| CAS No. | 89-25-8 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 35 mg/mL (200.9 mM) |
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| Water: <1 mg/mL |
| Ethanol: 35 mg/mL (200.9 mM) |
| SMILES | O=C1CC(C)=NN1C2=CC=CC=C2 |
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| Synonyms | MCI-186; NCI-C03952; MCI 186; NSC 12; MCI186; Radicut; trade name: Radicava; Methylphenylpyrazolone; Norantipyrine; Norphenazone; Phenylmethylpyrazolone; Arone
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实验参考方法
| In Vitro | In vitro activity: Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion.
Kinase Assay: Edaravone performs both preventative and therapeutic effects against toxicity of glutamate. Pretreatment of edaravone reduces the toxicity of glutamate towards SGNs. Edaravone reduces apoptosis and necrosis caused by glutamate. Pretreatment of edaravone (500 μM) reverses these changes to approximately normal levels. The protective effect of edaravone on SGNs against glutamate-induced apoptosis is associated with PI3K/Akt pathway and Bcl-2 protein family.
Cell Assay: Cell viability is quantified by MTT assay and trypan blue staining. MTT (5 mg/mL, 20 μL) is added to each well and incubated for 4 h at 37°C after the drug treatments. The medium is removed and the cell pellet is dissolved in DMSO. Then, the optical density (OD) values are measured at 570 nm using an ELISA reader. |
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| In Vivo | Edaravone significantly reduces the infarct volume and improves the neurological deficit scores at 24 hours after reperfusion in mice brain. Edaravone markedly suppresses the accumulation of HNE-modified protein and 8-OHdG at the penumbra area during the early period after reperfusion and reduces microglial activation, iNOS expression, and nitrotyrosine formation at the late period. Edaravone attenuates renal function and pathologic findings significantly in rat kidney. Edaravone significantly reduces the generation of free radicals in the tubular cells indicated by dichlorodihydrofluorescein. Edaravone-treated animals shows significantly improved neurological outcome. Edaravone-treatment provides a significant reduction in the number of TUNEL-positive apoptotic cells, a decrease in Bax immunoreactivity and an increase in Bcl-2 expression within the peri-infarct area. Edaravone shows an excellent neuroprotective effect against ischemia/reperfusion brain injury through a Bax/Bcl-2 dependent anti-apoptotic mechanism. |
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| Animal model | Mice and rats |
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| Formulation & Dosage | 20 mg/kg |
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| References | CNS Drug Rev. 2006 Spring;12(1):9-20; Stroke. 2005 Oct;36(10):2220-5. |
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