Edaravone
Identification
- Summary
Edaravone is a free radical scavenger used to delay the progression of ALS.
- Brand Names
- Radicava
- Generic Name
- Edaravone
- DrugBank Accession Number
- DB12243
- Background
Edaravone is a free radical scavenger approved in May, 2017 for the treatment of amyotrophic lateral scleorosis (ALS). Clinical studies showed that the treatment attenuated deterioration of the disease when compared to placebo. It has been previously investigated for the treatment of ischemic stroke, reperfusion Injury, and myocardial Infarction as it possesses antioxidant and anti-apoptotic properties. Being a low molecular weight molecule with good water and lipid-soluble properies, it is therapeutically advantageous in crossing the blood-brain barrier to mediate nootropic and neuroprotective effects. Oral formulation of edaravone is currently under development.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Edaravone (DB12243)
- Weight
- Average: 174.203
Monoisotopic: 174.07931295 - Chemical Formula
- C10H10N2O
- Synonyms
- 1-phenyl-3-methyl-5-oxo-2-pyrazoline
- 2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one
- 3-methyl-1-phenyl-2-pyrazolin-5-one
- 3-methyl-1-phenyl-5-pyrazolone
- 3-methyl-1-phenylpyrazol-5-one
- Edaravone
- Methylphenylpyrazolone
- Norphenazone
- Phenyl methyl pyrazolone
- Phenylmethylpyrazolone
- External IDs
- MCI-186
- NSC-12
- NSC-26139
- NSC-2629
- TW001
Pharmacology
- Indication
Indicated for improving neurological symptoms and damage from acute ischemic stroke and delaying disease progression of ALS.
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- Contraindications & Blackbox Warnings
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Edaravone scavenges free hydroxyl radicals and peroxynitrite radicals which are highly associated with neuronal damage/death from many cerebral vascular disorders such as ischemic strokes and degenerative neurological disorders such as ALS. It exerts a neuroprotective and antioxidant effect and delays disease progression by limiting the extent of lipid peroxidation via free radical generation and cell membrane damage from oxidative stress. It reversed the reduction in regional blood flow and cerebral edema in a case of ischemic stroke.
- Mechanism of action
Nootropic and neuroprotective effects are mediated through inhibiting lipid peroxidation and scavenging free radicals. Edaravone acts to increase prostacyclin production, decrease lipoxygenase metabolism of arachidonic acid by trapping hydroxyl radicals, and inhibit alloxan-induced lipid peroxidation and quench active oxygen species. It targets various kinds of cells, including neurons, endothelial cells and myocardial cells 6. There is also evidence of reduction of neuronal nitric oxide synthase (nNOS) levels and potentiation of SOD1 levels after transient ischemia in rabbits thus preventing spinal cord injury.
- Absorption
The peak plasma concentration of the parent drug is reached at the end of infusion, without accumulation of the drug with multiple dosing regimen. The mean Cmax value in healthy male adults is 888ng/mL for intravenous infusion. The values of AUC and Cmax are increased in a dose-proportional relationship. The oral bioavailability in mouse studies is 38% of the I.V. delivery 1.
- Volume of distribution
The mean Vd value following an intravenous infusion of a single 30mg dose is 18.5L/kg 2.
- Protein binding
The in vitro binding rates of edaravone to human serum protein and albumin are 92% and 89-91%, respectively, with no concentration-dependence.
- Metabolism
Multiple renal and hepatic uridine diphosphate glucuronosyltransferase (UGT) isoforms catalyze glucuronidation reaction of edaravone to form glucuronide conjugates. Edaravone is also metabolized into sulfate conjugates via sulfotransferase activity, which is the main metabolite form predominantly found circulating in plasma. It is predicted that the sulfate conjugate is hydrolyzed back to edaravone, which is then converted to the glucuronide conjugate in the human kidney before excretion into the urine. These metabolites have no pharmacological activity.
- Route of elimination
About 0.7-0.9% of the dose is excreted as unchanged drug and 71.0-79.9% of the dose is excreted as metabolites (mostly as glucuronide conjugates) through mainly renal elimination.
- Half-life
The mean terminal elimination half-life of edaravone is 4.5 to 6 hours and the half-lives of its metabolites are 2 to 2.8 hours.
- Clearance
The mean total plasma drug clearance following an intravenous infusion of a single 30mg dose is 0.1L/min 2.
- Adverse Effects
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No reported evidence of carcinogenic, mutagenic or teratogenic potential. Oral LD50 value is 1,915 mg/kg (Rat). Adverse effects include rashes, hypertension, altered hepatic function, and acute renal impairment. Hematological abnormalities, lung injury and rhabomyolysis may occur with no known incidences.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetazolamide The excretion of Edaravone can be decreased when combined with Acetazolamide. Acetylsalicylic acid The excretion of Edaravone can be decreased when combined with Acetylsalicylic acid. Acyclovir The excretion of Edaravone can be decreased when combined with Acyclovir. Adefovir dipivoxil The excretion of Edaravone can be decreased when combined with Adefovir dipivoxil. Alprostadil The excretion of Edaravone can be decreased when combined with Alprostadil. Aminohippuric acid The excretion of Edaravone can be decreased when combined with Aminohippuric acid. Aminophenazone The excretion of Edaravone can be decreased when combined with Aminophenazone. Amoxicillin The excretion of Edaravone can be decreased when combined with Amoxicillin. Antipyrine The excretion of Edaravone can be decreased when combined with Antipyrine. Apalutamide The excretion of Edaravone can be decreased when combined with Apalutamide. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Arone (Edinburgh Pharmaceuticals (India)) / Radicut (Mitsubishi Tanabe Pharma Corporation)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Radicava Injection 30 mg/100mL Intravenous Mitsubishi Tanabe Pharma America, Inc. 2017-05-05 Not applicable US 
Radicava Solution 30 mg / 100 mL Intravenous Mitsubishi Tanabe Pharma Corporation 2019-10-29 Not applicable Canada 
Radicava Injection 60 mg/100mL Intravenous Mitsubishi Tanabe Pharma America, Inc. 2020-05-05 Not applicable US
Categories
- ATC Codes
- N07XX14 — Edaravone
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrazolones. These are compounds containing a pyrazole ring which bears a ketone.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azolines
- Sub Class
- Pyrazolines
- Direct Parent
- Pyrazolones
- Alternative Parents
- Benzene and substituted derivatives / Carboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- ring assembly (CHEBI:31530)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- S798V6YJRP
- CAS number
- 89-25-8
- InChI Key
- QELUYTUMUWHWMC-UHFFFAOYSA-N
- InChI
- InChI=1S/C10H10N2O/c1-8-7-10(13)12(11-8)9-5-3-2-4-6-9/h2-6H,7H2,1H3
- IUPAC Name
- 3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one
- SMILES
- CC1=NN(C(=O)C1)C1=CC=CC=C1
References
- General References
- Jiao SS, Yao XQ, Liu YH, Wang QH, Zeng F, Lu JJ, Liu J, Zhu C, Shen LL, Liu CH, Wang YR, Zeng GH, Parikh A, Chen J, Liang CR, Xiang Y, Bu XL, Deng J, Li J, Xu J, Zeng YQ, Xu X, Xu HW, Zhong JH, Zhou HD, Zhou XF, Wang YJ: Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits. Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5225-30. doi: 10.1073/pnas.1422998112. Epub 2015 Apr 6. [Article]
- Li H, Xu K, Wang Y, Zhang H, Li T, Meng L, Gong X, Zhang H, Ou N, Ruan J: Phase I clinical study of edaravone in healthy Chinese volunteers: safety and pharmacokinetics of single or multiple intravenous infusions. Drugs R D. 2012 Jun 1;12(2):65-70. doi: 10.2165/11634290-000000000-00000. [Article]
- Watanabe T, Tahara M, Todo S: The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther. 2008 Summer;26(2):101-14. doi: 10.1111/j.1527-3466.2008.00041.x. [Article]
- Kikuchi K, Uchikado H, Miyagi N, Morimoto Y, Ito T, Tancharoen S, Miura N, Miyata K, Sakamoto R, Kikuchi C, Iida N, Shiomi N, Kuramoto T, Kawahara K: Beyond neurological disease: new targets for edaravone (Review). Int J Mol Med. 2011 Dec;28(6):899-906. doi: 10.3892/ijmm.2011.795. Epub 2011 Sep 15. [Article]
- Kikuchi K, Miura N, Kawahara KI, Murai Y, Morioka M, Lapchak PA, Tanaka E: Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke. Biomed Rep. 2013 Jan;1(1):7-12. Epub 2012 Aug 29. [Article]
- Ikeda K, Iwasaki Y: Edaravone, a Free Radical Scavenger, Delayed Symptomatic and Pathological Progression of Motor Neuron Disease in the Wobbler Mouse. PLoS One. 2015 Oct 15;10(10):e0140316. doi: 10.1371/journal.pone.0140316. eCollection 2015. [Article]
- Mitsubishi Tanabe Pharma Corporation Radicut Label [Link]
- FDA Approved Drug Products: RADICAVA (edaravone) injection [Link]
- External Links
- PDB Entries
- 5s3i / 5s52
- FDA label
- Download (193 KB)
- MSDS
- Download (27.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Cerebral Infarctions 1 4 Completed Treatment Cerebrovascular Accident 1 4 Completed Treatment Myocardial Infarction / Reperfusion Injury 1 3 Active Not Recruiting Treatment Amyotrophic Lateral Sclerosis (ALS) 1 3 Completed Treatment Amyotrophic Lateral Sclerosis (ALS) 4 3 Completed Treatment Stroke, Acute, Stroke Ischemic 1 3 Recruiting Treatment Amyotrophic Lateral Sclerosis (ALS) 2 2 Completed Treatment Brain Necrosis / Nasopharyngeal Carcinoma (NPC) 1 2 Completed Treatment Stroke, Acute, Stroke Ischemic 2 2 Not Yet Recruiting Treatment Amyotrophic Lateral Sclerosis (ALS) / Respiratory Functions / Scopolamine 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 30 mg/100mL Injection Intravenous 60 mg/100mL Injection, solution, concentrate Intravenous Solution Intravenous 30 mg / 100 mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6933310 No 2005-08-23 2020-11-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 129.7 FDA Label water solubility <1 mg/mL MSDS pKa 7.0 Watanabe T, Tahara M, Todo S: The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther. 2008 Summer;26(2):101-14. doi: 10.1111/j.1527-3466.2008.00041.x. [A19140] - Predicted Properties
Property Value Source Water Solubility 0.939 mg/mL ALOGPS logP 0.53 ALOGPS logP 1.53 ChemAxon logS -2.3 ALOGPS pKa (Strongest Acidic) 13.45 ChemAxon pKa (Strongest Basic) -1.5 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 32.67 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 49.49 m3·mol-1 ChemAxon Polarizability 18.61 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-004i-1900000000-9c17dd936441a10926dc
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Substrate profile was investigated in vitro using HEK293 cells.
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Substrate activity was demonstrated in vitro using HEK293 cells.
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
Drug created on October 20, 2016 21:42 / Updated on October 19, 2021 07:39