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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Drug Repurposing: Promises of Edaravone Target Drug in Traumatic Brain Injury

Author(s): Zaynab Shakkour, Hawraa Issa, Helene Ismail, Ohanes Ashekyan, Karl John Habashy, Leila Nasrallah, Hussam Jourdi, Eva Hamade, Stefania Mondello, Mirna Sabra*, Kazem Zibara* and Firas Kobeissy*

Volume 28, Issue 12, 2021

Published on: 12 August, 2020

Page: [2369 - 2391] Pages: 23

DOI: 10.2174/0929867327666200812221022

Price: $65


Edaravone is a potent free-radical scavenger that has been in the market for more than 30 years. It was originally developed in Japan to treat strokes and has been used there since 2001. Aside from its anti-oxidative effects, edaravone demonstrated beneficial effects on proinflammatory responses, nitric oxide production, and apoptotic cell death. Interestingly, edaravone has shown neuroprotective effects in several animal models of diseases other than stroke. In particular, edaravone administration was found to be effective in halting amyotrophic lateral sclerosis (ALS) progression during the early stages. Accordingly, after its success in Phase III clinical studies, edaravone has been approved by the FDA as a treatment for ALS patients. Considering its promises in neurological disorders and its safety in patients, edaravone is a drug of interest that can be repurposed for traumatic brain injury (TBI) treatment. Drug repurposing is a novel approach in drug development that identifies drugs for purposes other than their original indication. This review presents the biochemical properties of edaravone along with its effects on several neurological disorders in the hope that it can be adopted for treating TBI patients.

Keywords: Traumatic Brain Injury (TBI), drug repurposing, edaravone, amyotrophic lateral sclerosis, stroke, neurological disorders.

Abe, K.; Yuki, S.; Kogure, K. Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger. Stroke, 1988, 19(4), 480-485.
[] [PMID: 2834836]
Kikuchi, K.; Miura, N.; Kawahara, K.I.; Murai, Y.; Morioka, M.; Lapchak, P.A.; 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, 1(1), 7-12.
[] [PMID: 24648884]
Adams, H.P. Jr.; del Zoppo, G.; Alberts, M.J.; Bhatt, D.L.; Brass, L.; Furlan, A.; Grubb, R.L.; Higashida, R.T.; Jauch, E.C.; Kidwell, C.; Lyden, P.D.; Morgenstern, L.B.; Qureshi, A.I.; Rosenwasser, R.H.; Scott, P.A.; Wijdicks, E.F.M.; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Guidelines for the early management of adults with ischemic stroke: a guideline from the American heart association/American stroke association stroke council, clinical cardiology council, cardiovascular radiology and intervention council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: the American Academy of neurology affirms the value of this guideline as an educational tool for neurologists. Stroke, 2007, 38(5), 1655-1711.
[] [PMID: 17431204]
Watanabe, K.; Tanaka, M.; Yuki, S.; Hirai, M.; Yamamoto, Y. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J. Clin. Biochem. Nutr., 2018, 62(1), 20-38.
[] [PMID: 29371752]
Higashi, Y.; Jitsuiki, D.; Chayama, K.; Yoshizumi, M. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger, for treatment of cardiovascular diseases. Recent Pat. Cardiovasc. Drug Discov., 2006, 1(1), 85-93.
[] [PMID: 18221078]
Parikh, A.; Kathawala, K.; Tan, C.C.; Garg, S.; Zhou, X.F. Self-nanomicellizing solid dispersion of edaravone: part I - oral bioavailability improvement. Drug Des. Devel. Ther., 2018, 12, 2051-2069.
[] [PMID: 30013324]
Takei, K.; Watanabe, K.; Yuki, S.; Akimoto, M.; Sakata, T.; Palumbo, J. Edaravone and its clinical development for amyotrophic lateral sclerosis. Amyotroph. Lateral. Scler. Frontotemporal Degener., 2017, 18(sup1), 5-10.
[] [PMID: 28872907]
Bailly, C. Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers. Int. Immunopharmacol., 2019, 77, 105967.
[] [PMID: 31670091]
Marković, V.; Erić, S.; Juranić, Z.D.; Stanojković, T.; Joksović, L.; Ranković, B.; Kosanić, M.; Joksović, M.D. Synthesis, antitumor activity and QSAR studies of some 4-aminomethylidene derivatives of edaravone. Bioorg. Chem., 2011, 39(1), 18-27.
[] [PMID: 21078519]
Lapchak, P.A. A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy? Expert Opin. Pharmacother., 2010, 11(10), 1753-1763.
[] [PMID: 20491547]
Yoshida, H.; Sasaki, K.; Namiki, Y.; Sato, N.; Tada, N. Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase. Atherosclerosis, 2005, 179(1), 97-102.
[] [PMID: 15721014]
Yamamoto, Y. Plasma marker of tissue oxidative damage and edaravone as a scavenger drug against peroxyl radicals and peroxynitrite. J. Clin. Biochem. Nutr., 2017, 60(1), 49-54.
[] [PMID: 28163382]
Higashi, Y. Edaravone for the treatment of acute cerebral infarction: role of endothelium-derived nitric oxide and oxidative stress. Expert Opin. Pharmacother., 2009, 10(2), 323-331.
[] [PMID: 19236202]
Banno, M.; Mizuno, T.; Kato, H.; Zhang, G.; Kawanokuchi, J.; Wang, J.; Kuno, R.; Jin, S.; Takeuchi, H.; Suzumura, A. The radical scavenger edaravone prevents oxidative neurotoxicity induced by peroxynitrite and activated microglia. Neuropharmacology, 2005, 48(2), 283-290.
[] [PMID: 15695167]
Watanabe, T.; Tahara, M.; Todo, S. The novel antioxidant edaravone: from bench to bedside. Cardiovasc. Ther., 2008, 26(2), 101-114.
[] [PMID: 18485133]
Park, H.J.; Lee, H.J.; Choi, M.S.; Son, D.J.; Song, H.S.; Song, M.J.; Lee, J.M.; Han, S.B.; Kim, Y.; Hong, J.T. JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin. J. Inflamm. (Lond.), 2008, 5, 7.
[] [PMID: 18507870]
Dhanasekaran, D.N.; Reddy, E.P. JNK signaling in apoptosis. Oncogene, 2008, 27(48), 6245-6251.
[] [PMID: 18931691]
Kikuchi, K.; Kawahara, K-I.; Uchikado, H.; Miyagi, N.; Kuramoto, T.; Miyagi, T.; Morimoto, Y.; Ito, T.; Tancharoen, S.; Miura, N.; Takenouchi, K.; Oyama, Y.; Shrestha, B.; Matsuda, F.; Yoshida, Y.; Arimura, S.; Mera, K.; Tada, K-I.; Yoshinaga, N.; Maenosono, R.; Ohno, Y.; Hashiguchi, T.; Maruyama, I.; Shigemori, M. Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction. Exp. Ther. Med., 2011, 2(5), 771-775.
[] [PMID: 22977573]
Katan, M.; Luft, A. Global burden of stroke. Semin. Neurol., 2018, 38(2), 208-211.
[] [PMID: 29791947]
Liang, D.; Bhatta, S.; Gerzanich, V.; Simard, J.M. Cytotoxic edema: mechanisms of pathological cell swelling. Neurosurg. Focus, 2007, 22(5), E2.
[] [PMID: 17613233]
Abramov, A.Y.; Scorziello, A.; Duchen, M.R. Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation. J. Neurosci., 2007, 27(5), 1129-1138.
[] [PMID: 17267568]
Shi, K.; Tian, D.C.; Li, Z.G.; Ducruet, A.F.; Lawton, M.T.; Shi, F.D. Global brain inflammation in stroke. Lancet Neurol., 2019, 18(11), 1058-1066.
[] [PMID: 31296369]
Jiang, X.; Andjelkovic, A.V.; Zhu, L.; Yang, T.; Bennett, M.V.L.; Chen, J.; Keep, R.F.; Shi, Y. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog. Neurobiol., 2018, 163-164, 144-171.
[] [PMID: 28987927]
Rodrigo, R.; Fernández-Gajardo, R.; Gutiérrez, R.; Matamala, J.M.; Carrasco, R.; Miranda-Merchak, A.; Feuerhake, W. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. CNS Neurol. Disord. Drug Targets, 2013, 12(5), 698-714.
[] [PMID: 23469845]
Keep, R.F.; Zhou, N.; Xiang, J.; Andjelkovic, A.V.; Hua, Y.; Xi, G. Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage. Fluids Barriers CNS, 2014, 11, 18.
[] [PMID: 25120903]
Saver, J.L. Time is brain--quantified. Stroke, 2006, 37(1), 263-266.
[] [PMID: 16339467]
Bhatia, R.; Hill, M.D.; Shobha, N.; Menon, B.; Bal, S.; Kochar, P.; Watson, T.; Goyal, M.; Demchuk, A.M. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke, 2010, 41(10), 2254-2258.
[] [PMID: 20829513]
Rha, J.H.; Saver, J.L. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke, 2007, 38(3), 967-973.
[] [PMID: 17272772]
Hacke, W.; Albers, G.; Al-Rawi, Y.; Bogousslavsky, J.; Davalos, A.; Eliasziw, M.; Fischer, M.; Furlan, A.; Kaste, M.; Lees, K.R.; Soehngen, M.; Warach, S. The desmoteplase in acute ischemic stroke trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke, 2005, 36(1), 66-73.
[] [PMID: 15569863]
English, J.D.; Yavagal, D.R.; Gupta, R.; Janardhan, V.; Zaidat, O.O.; Xavier, A.R.; Nogueira, R.G.; Kirmani, J.F.; Jovin, T.G. Mechanical thrombectomy-ready comprehensive stroke center requirements and endovascular stroke systems of care: recommendations from the endovascular stroke standards committee of the society of vascular and interventional neurology (SVIN). Intervent. Neurol., 2016, 4(3-4), 138-150.
[] [PMID: 27051410]
Yoshida, H.; Yanai, H.; Namiki, Y.; Fukatsu-Sasaki, K.; Furutani, N.; Tada, N. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev., 2006, 12(1), 9-20.
[] [PMID: 16834755]
Fujiwara, N.; Som, A.T.; Pham, L.D.; Lee, B.J.; Mandeville, E.T.; Lo, E.H.; Arai, K. A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model. Neurosci. Lett., 2016, 633, 7-13.
[] [PMID: 27589890]
Zhang, N.; Komine-Kobayashi, M.; Tanaka, R.; Liu, M.; Mizuno, Y.; Urabe, T. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke, 2005, 36(10), 2220-2225.
[] [PMID: 16166574]
Wen, J.; Watanabe, K.; Ma, M.; Yamaguchi, K.; Tachikawa, H.; Kodama, M.; Aizawa, Y. Edaravone inhibits JNK-c-Jun pathway and restores anti-oxidative defense after ischemia-reperfusion injury in aged rats. Biol. Pharm. Bull., 2006, 29(4), 713-718.
[] [PMID: 16595905]
Kikuchi, K.; Tancharoen, S.; Matsuda, F.; Biswas, K.K.; Ito, T.; Morimoto, Y.; Oyama, Y.; Takenouchi, K.; Miura, N.; Arimura, N.; Nawa, Y.; Meng, X.; Shrestha, B.; Arimura, S.; Iwata, M.; Mera, K.; Sameshima, H.; Ohno, Y.; Maenosono, R.; Tajima, Y.; Uchikado, H.; Kuramoto, T.; Nakayama, K.; Shigemori, M.; Yoshida, Y.; Hashiguchi, T.; Maruyama, I.; Kawahara, K. Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem. Biophys. Res. Commun., 2009, 390(4), 1121-1125.
[] [PMID: 19737535]
Nakamura, T.; Kuroda, Y.; Yamashita, S.; Zhang, X.; Miyamoto, O.; Tamiya, T.; Nagao, S.; Xi, G.; Keep, R.F.; Itano, T. Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke, 2008, 39(2), 463-469.
[] [PMID: 18096835]
Ishikawa, A.; Yoshida, H.; Metoki, N.; Toki, T.; Imaizumi, T.; Matsumiya, T.; Yamashita, K.; Taima, K.; Satoh, K. Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Neurosci. Res., 2007, 59(4), 406-412.
[] [PMID: 17889387]
Otani, H.; Togashi, H.; Jesmin, S.; Sakuma, I.; Yamaguchi, T.; Matsumoto, M.; Kakehata, H.; Yoshioka, M. Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus. Eur. J. Pharmacol., 2005, 512(2-3), 129-137.
[] [PMID: 15840397]
Yokota, S.; Kumagai, Y.; Uchiumi, M.; Isawa, S.; Murasaki, M.; Akimoto, K.; Iwamoto, M.; Yuasa, T.; Iwano, M. A pharmacokinetic study of MCI-186, a novel drug for cerebrovascular disease in elderly and young healthy subjects. Japan. J. Clin. Pharmacol Therapeu., 1997, 28(3), 693-702.
Edaravone Acute Infarction Study Group. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc. Dis., 2003, 15(3), 222-229.
[] [PMID: 12715790]
Toyoda, K.; Fujii, K.; Kamouchi, M.; Nakane, H.; Arihiro, S.; Okada, Y.; Ibayashi, S.; Iida, M. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. J. Neurol. Sci., 2004, 221(1-2), 11-17.
[] [PMID: 15178207]
Ogasawara, K.; Yamadate, K.; Kobayashi, M.; Endo, H.; Fukuda, T.; Yoshida, K.; Terasaki, K.; Inoue, T.; Ogawa, A. Effects of the free radical scavenger, edaravone, on the development of postoperative cognitive impairment in patients undergoing carotid endarterectomy. Surg. Neurol., 2005, 64(4), 309-313.
[] [PMID: 16182000]
Uno, M.; Kitazato, K.T.; Suzue, A.; Matsuzaki, K.; Harada, M.; Itabe, H.; Nagahiro, S. Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction. Free Radic. Biol. Med., 2005, 39(8), 1109-1116.
[] [PMID: 16198237]
Imai, K.; Mori, T.; Izumoto, H.; Takabatake, N.; Kunieda, T.; Watanabe, M. Hyperbaric oxygen combined with intravenous edaravone for treatment of acute embolic stroke: a pilot clinical trial. Neurol. Med. Chir. (Tokyo), 2006, 46(8), 373-378.
[] [PMID: 16936457]
Munakata, A.; Ohkuma, H.; Nakano, T.; Shimamura, N.; Asano, K.; Naraoka, M. Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery, 2009, 64(3), 423-428.
[] [PMID: 19240603]
Shinohara, Y.; Saito, I.; Kobayashi, S.; Uchiyama, S. Edaravone (radical scavenger) versus sodium ozagrel (antiplatelet agent) in acute noncardioembolic ischemic stroke (EDO trial). Cerebrovasc. Dis., 2009, 27(5), 485-492.
[] [PMID: 19321945]
Naritomi, H.; Moriwaki, H.; Metoki, N.; Nishimura, H.; Higashi, Y.; Yamamoto, Y.; Yuasa, H.; Oe, H.; Tanaka, K.; Saito, K.; Terayama, Y.; Oda, T.; Tanahashi, N.; Kondo, H. Effects of edaravone on muscle atrophy and locomotor function in patients with ischemic stroke: a randomized controlled pilot study. Drugs R D., 2010, 10(3), 155-163.
[] [PMID: 20945946]
Nakase, T.; Yoshioka, S.; Suzuki, A. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke. BMC Neurol., 2011, 11, 39.
[] [PMID: 21447190]
Sharma, P.; Sinha, M.; Shukla, R.; Garg, R.K.; Verma, R.; Singh, M.K. A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke. Ann. Indian Acad. Neurol., 2011, 14(2), 103-106.
[] [PMID: 21808471]
Kimura, K.; Aoki, J.; Sakamoto, Y.; Kobayashi, K.; Sakai, K.; Inoue, T.; Iguchi, Y.; Shibazaki, K. Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients--a preliminary study. J. Neurol. Sci., 2012, 313(1-2), 132-136.
[] [PMID: 21967833]
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, 12(2), 65-70.
[] [PMID: 22762844]
Kaste, M.; Murayama, S.; Ford, G.A.; Dippel, D.W.; Walters, M.R.; Tatlisumak, T. Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute ischemic stroke: new formulation and dosing regimen. Cerebrovasc. Dis., 2013, 36(3), 196-204.
[] [PMID: 24135530]
Zheng, J.; Chen, X. Edaravone offers neuroprotection for acute diabetic stroke patients. Ir. J. Med. Sci., 2016, 185(4), 819-824.
[] [PMID: 26597952]
Aoki, J.; Kimura, K.; Morita, N.; Harada, M.; Metoki, N.; Tateishi, Y.; Todo, K.; Yamagami, H.; Hayashi, K.; Terasawa, Y.; Fujita, K.; Yamamoto, N.; Deguchi, I.; Tanahashi, N.; Inoue, T.; Iwanaga, T.; Kaneko, N.; Mitsumura, H.; Iguchi, Y.; Ueno, Y.; Kuramoto, Y.; Ogata, T.; Fujimoto, S.; Yokoyama, M.; Nagahiro, S. YAMATO Study (tissue-type plasminogen activator and edaravone combination therapy). Stroke, 2017, 48(3), 712-719.
[] [PMID: 28119434]
Sun, Z.; Xu, Q.; Gao, G.; Zhao, M.; Sun, C. Clinical observation in edaravone treatment for acute cerebral infarction. Niger. J. Clin. Pract., 2019, 22(10), 1324-1327.
[] [PMID: 31607719]
Kong, Z.; Jiang, J.; Deng, M.; Zhang, Z.; Wang, G. Edaravone reduces depression severity in patients with symptomatic intracranial stenosis and is associated with the serum expression of sex hormones. Medicine (Baltimore), 2020, 99(8), e19316.
[] [PMID: 32080148]
Yagi, K.; Kitazato, K.T.; Uno, M.; Tada, Y.; Kinouchi, T.; Shimada, K.; Nagahiro, S. Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke, 2009, 40(2), 626-631.
[] [PMID: 19095969]
Lapchak, P.A. Development of thrombolytic therapy for stroke: a perspective. Expert Opin. Investig. Drugs, 2002, 11(11), 1623-1632.
[] [PMID: 12437508]
Miyaji, Y.; Yoshimura, S.; Sakai, N.; Yamagami, H.; Egashira, Y.; Shirakawa, M.; Uchida, K.; Kageyama, H.; Tomogane, Y. Effect of edaravone on favorable outcome in patients with acute cerebral large vessel occlusion: subanalysis of RESCUE-Japan Registry. Neurol. Med. Chir. (Tokyo), 2015, 55(3), 241-247.
[] [PMID: 25739433]
Takenaka, K.; Kato, M.; Yamauti, K.; Hayashi, K. Simultaneous administration of recombinant tissue plasminogen activator and edaravone in acute cerebral ischemic stroke patients. J. Stroke Cerebrovasc. Dis., 2014, 23(10), 2748-2752.
[] [PMID: 25307430]
Sun, Y.Y.; Morozov, Y.M.; Yang, D.; Li, Y.; Dunn, R.S.; Rakic, P.; Chan, P.H.; Abe, K.; Lindquist, D.M.; Kuan, C.Y. Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke. PLoS One, 2014, 9(6), e98807.
[] [PMID: 24911517]
Kikuchi, K.; Setoyama, K.; Kawahara, K.I.; Nagasato, T.; Terashi, T.; Ueda, K.; Nakanishi, K.; Otsuka, S.; Miura, N.; Sameshima, H.; Hosokawa, K.; Harada, Y.; Shrestha, B.; Yamamoto, M.; Morimoto-Yamashita, Y.; Kikuchi, H.; Kiyama, R.; Kamikokuryo, C.; Tancharoen, S.; Sakakima, H.; Morioka, M.; Tanaka, E.; Ito, T.; Maruyama, I. Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombolysis. Oxid. Med. Cell. Longev., 2017, 2017, 6873281.
[] [PMID: 29259732]
Wada, T.; Yasunaga, H.; Inokuchi, R.; Horiguchi, H.; Fushimi, K.; Matsubara, T.; Nakajima, S.; Yahagi, N. Effects of edaravone on early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator. J. Neurol. Sci., 2014, 345(1-2), 106-111.
[] [PMID: 25085762]
Enomoto, M.; Endo, A.; Yatsushige, H.; Fushimi, K.; Otomo, Y. Clinical Effects of Early Edaravone Use in Acute Ischemic Stroke Patients Treated by Endovascular Reperfusion Therapy. Stroke, 2019, 50(3), 652-658.
[] [PMID: 30741623]
Rolain, H.; Miranpuri, G.S.; Ahmed, A.S. Edaravone’s antioxidant capabilities and its therapeutic benefits for post-ischemic stroke: a mini review. On J Complement & Alt Med., 2019, 2(4), e101752366.
Yuan, W.J.; Yasuhara, T.; Shingo, T.; Muraoka, K.; Agari, T.; Kameda, M.; Uozumi, T.; Tajiri, N.; Morimoto, T.; Jing, M.; Baba, T.; Wang, F.; Leung, H.; Matsui, T.; Miyoshi, Y.; Date, I. Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons. BMC Neurosci., 2008, 9, 75.
[] [PMID: 18671880]
Xiong, N.; Xiong, J.; Khare, G.; Chen, C.; Huang, J.; Zhao, Y.; Zhang, Z.; Qiao, X.; Feng, Y.; Reesaul, H.; Zhang, Y.; Sun, S.; Lin, Z.; Wang, T. Edaravone guards dopamine neurons in a rotenone model for Parkinson’s disease. PLoS One, 2011, 6(6), e20677.
[] [PMID: 21677777]
Bandookwala, M.; Sahu, A.K.; Thakkar, D.; Sharma, M.; Khairnar, A.; Sengupta, P. Edaravone-caffeine combination for the effective management of rotenone induced Parkinson’s disease in rats: an evidence based affirmative from a comparative analysis of behavior and biomarker expression. Neurosci. Lett., 2019, 711, 134438.
[] [PMID: 31422100]
Aoyama, T.; Hida, K.; Kuroda, S.; Seki, T.; Yano, S.; Shichinohe, H.; Iwasaki, Y. Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue damage in the murine spinal cord injury model. Neurol. Med. Chir. (Tokyo), 2008, 48(12), 539-545.
[] [PMID: 19106491]
Takahashi, G.; Sakurai, M.; Abe, K.; Itoyama, Y.; Tabayashi, K. MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits. J. Thorac. Cardiovasc. Surg., 2003, 126(5), 1461-1466.
[] [PMID: 14666020]
Ozgiray, E.; Serarslan, Y.; Oztürk, O.H.; Altaş, M.; Aras, M.; Söğüt, S.; Yurtseven, T.; Oran, I.; Zileli, M. Protective effects of edaravone on experimental spinal cord injury in rats. Pediatr. Neurosurg., 2011, 47(4), 254-260.
[] [PMID: 22310070]
Takahashi, G.; Sakurai, M.; Abe, K.; Itoyama, Y.; Tabayashi, K. MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia. Ann. Thorac. Surg., 2004, 78(2), 602-607.
[] [PMID: 15276530]
Ohta, S.; Iwashita, Y.; Takada, H.; Kuno, S.; Nakamura, T. Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats. Spine, 2005, 30(10), 1154-1158.
[] [PMID: 15897829]
Zhang, T.; Li, Z.; Dong, J.; Nan, F.; Li, T.; Yu, Q. Edaravone promotes functional recovery after mechanical peripheral nerve injury. Neural Regen. Res., 2014, 9(18), 1709-1715.
[] [PMID: 25374594]
Zhang, S.Q.; Wu, M.F.; Piao, Z.; Yao, J.; Li, J.H.; Wang, X.G.; Liu, J. Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats. Neural Regen. Res., 2015, 10(2), 230-236.
[] [PMID: 25883621]
Garg, S.; Chaudhari, D.; Renjen, P.; Mishra, A.; Kumar, A.; Pradhan, R. Edaravone: A new hope for patients with amyotrophic lateral sclerosis. Apollo Medicine, 2019, 16(3), 157-160.
Mehta, P.; Kaye, W.; Raymond, J.; Wu, R.; Larson, T.; Punjani, R.; Heller, D.; Cohen, J.; Peters, T.; Muravov, O.; Horton, K. Prevalence of amyotrophic lateral sclerosis - United States, 2014. MMWR Morb. Mortal. Wkly. Rep., 2018, 67(7), 216-218.
[] [PMID: 29470458]
Barber, S.C.; Shaw, P.J. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic. Biol. Med., 2010, 48(5), 629-641.
[] [PMID: 19969067]
Veyrat-Durebex, C.; Corcia, P.; Piver, E.; Devos, D.; Dangoumau, A.; Gouel, F.; Vourc’h, P.; Emond, P.; Laumonnier, F.; Nadal-Desbarats, L.; Gordon, P.H.; Andres, C.R.; Blasco, H. Disruption of TCA cycle and glutamate metabolism identified by metabolomics in an in vitro model of amyotrophic lateral sclerosis. Mol. Neurobiol., 2016, 53(10), 6910-6924.
[] [PMID: 26666663]
Park, J.M.; Kim, S.Y.; Park, D.; Park, J.S. Effect of edaravone therapy in Korean amyotrophic lateral sclerosis (ALS) patients. Neurol. Sci., 2020, 41(1), 119-123.
[] [PMID: 31471712]
Cruz, M.P. Edaravone (radicava): a novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis. P&T, 2018, 43(1), 25-28.
[PMID: 29290672]
Bensimon, G.; Lacomblez, L.; Meininger, V. A controlled trial of riluzole in amyotrophic lateral sclerosis. N. Engl. J. Med., 1994, 330(9), 585-591.
[] [PMID: 8302340]
Yoshino, H. Edaravone for the treatment of amyotrophic lateral sclerosis. Expert Rev. Neurother., 2019, 19(3), 185-193.
[] [PMID: 30810406]
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, 10(10), e0140316.
[] [PMID: 26469273]
Aoki, M.; Warita, H.; Mizuno, H.; Suzuki, N.; Yuki, S.; Itoyama, Y. Feasibility study for functional test battery of SOD transgenic rat (H46R) and evaluation of edaravone, a free radical scavenger. Brain Res., 2011, 1382, 321-325.
[] [PMID: 21276427]
Ito, H.; Wate, R.; Zhang, J.; Ohnishi, S.; Kaneko, S.; Ito, H.; Nakano, S.; Kusaka, H. Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Exp. Neurol., 2008, 213(2), 448-455.
[] [PMID: 18718468]
Yamamoto, T.; Yuki, S.; Watanabe, T.; Mitsuka, M.; Saito, K.I.; Kogure, K. Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia. Brain Res., 1997, 762(1-2), 240-242.
[] [PMID: 9262182]
Jaiswal, M.K. Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs. Med. Res. Rev., 2019, 39(2), 733-748.
[] [PMID: 30101496]
Sawada, H. Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis. Expert Opin. Pharmacother., 2017, 18(7), 735-738.
[] [PMID: 28406335]
Cedarbaum, J.M.; Stambler, N.; Malta, E.; Fuller, C.; Hilt, D.; Thurmond, B.; Nakanishi, A. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J. Neurol. Sci., 1999, 169(1-2), 13-21.
[] [PMID: 10540002]
Beydoun, S.R.; Rosenfeld, J. Edaravone in amyotrophic lateral sclerosis—lessons from the clinical development program and the importance of a strategic clinical trial design. US Neurol., 2018, 14(1), 47-53.
Yoshino, H.; Kimura, A. Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study). Amyotroph. Lateral Scler., 2006, 7(4), 241-245.
[] [PMID: 17127563]
Abe, K.; Itoyama, Y.; Sobue, G.; Tsuji, S.; Aoki, M.; Doyu, M.; Hamada, C.; Kondo, K.; Yoneoka, T.; Akimoto, M.; Yoshino, H. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph. Lateral Scler. Frontotemporal Degener., 2014, 15(7-8), 610-617.
[] [PMID: 25286015]
Writing Group- Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol., 2017, 16(7), 505-512.
[] [PMID: 28522181]
Edaravone (MCI-186) ALS 16 Study Group. A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener, 2017, 18(sup1), 11-19.
[] [PMID: 28872917]
Castrillo-Viguera, C.; Grasso, D.L.; Simpson, E.; Shefner, J.; Cudkowicz, M.E. Clinical significance in the change of decline in ALSFRS-R. Amyotroph. Lateral Scler., 2010, 11(1-2), 178-180.
[] [PMID: 19634063]
Writing Group On Behalf of the Edaravone (MCI-186) ALS 19 Study Group. Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener, 2017, 18(sup1), 55-63.
[] [PMID: 28872920]
Shefner, J.; Heiman-Patterson, T.; Pioro, E.P.; Wiedau-Pazos, M.; Liu, S.; Zhang, J.; Agnese, W.; Apple, S. Long-term edaravone efficacy in amyotrophic lateral sclerosis: post-hoc analyses of study 19 (MCI186-19). Muscle Nerve, 2020, 61(2), 218-221.
[] [PMID: 31621933]
Scannell, J.W.; Blanckley, A.; Boldon, H.; Warrington, B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat. Rev. Drug Discov., 2012, 11(3), 191-200.
[] [PMID: 22378269]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[] [PMID: 30310233]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[] [PMID: 15286734]
Munos, B. Lessons from 60 years of pharmaceutical innovation. Nat. Rev. Drug Discov., 2009, 8(12), 959-968.
[] [PMID: 19949401]
Nosengo, N. Can you teach old drugs new tricks? Nature, 2016, 534(7607), 314-316.
[] [PMID: 27306171]
Stein, D.G.; Sayeed, I. Repurposing and repositioning neurosteroids in the treatment of traumatic brain injury: a report from the trenches. Neuropharmacology, 2019, 147, 66-73.
[] [PMID: 29630902]
DeWitt, D.S.; Hawkins, B.E.; Dixon, C.E.; Kochanek, P.M.; Armstead, W.; Bass, C.R.; Bramlett, H.M.; Buki, A.; Dietrich, W.D.; Ferguson, A.R.; Hall, E.D.; Hayes, R.L.; Hinds, S.R.; LaPlaca, M.C.; Long, J.B.; Meaney, D.F.; Mondello, S.; Noble-Haeusslein, L.J.; Poloyac, S.M.; Prough, D.S.; Robertson, C.S.; Saatman, K.E.; Shultz, S.R.; Shear, D.A.; Smith, D.H.; Valadka, A.B.; VandeVord, P.; Zhang, L. Pre-clinical testing of therapies for traumatic brain injury. J. Neurotrauma, 2018, 35(23), 2737-2754.
[] [PMID: 29756522]
Gooch, C.L.; Pracht, E.; Borenstein, A.R. The burden of neurological disease in the United States: a summary report and call to action. Ann. Neurol., 2017, 81(4), 479-484.
[] [PMID: 28198092]
Clausen, F.; Lundqvist, H.; Ekmark, S.; Lewén, A.; Ebendal, T.; Hillered, L. Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury. J. Neurotrauma, 2004, 21(9), 1168-1182.
[] [PMID: 15453987]
Miyamoto, N.; Maki, T.; Pham, L.D.; Hayakawa, K.; Seo, J.H.; Mandeville, E.T.; Mandeville, J.B.; Kim, K.W.; Lo, E.H.; Arai, K. Oxidative stress interferes with white matter renewal after prolonged cerebral hypoperfusion in mice. Stroke, 2013, 44(12), 3516-3521.
[] [PMID: 24072001]
Yuan, Y.; Zha, H.; Rangarajan, P.; Ling, E.A.; Wu, C. Anti-inflammatory effects of edaravone and scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci., 2014, 15, 125.
[] [PMID: 25416145]
Shen, Y.; Liu, X.B.; Pleasure, D.E.; Deng, W. Axon-glia synapses are highly vulnerable to white matter injury in the developing brain. J. Neurosci. Res., 2012, 90(1), 105-121.
[] [PMID: 21812016]
Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, M.C.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C. A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials. Sci. Rep., 2017, 7, 45780.
[] [PMID: 28387380]
Gean, A.D.; Fischbein, N.J. Head trauma. Neuroimaging Clin. N. Am., 2010, 20(4), 527-556.
[] [PMID: 20974375]
Saatman, K.E.; Duhaime, A.C.; Bullock, R.; Maas, A.I.; Valadka, A.; Manley, G.T. Classification of traumatic brain injury for targeted therapies. J. Neurotrauma, 2008, 25(7), 719-738.
[] [PMID: 18627252]
Bigler, E.D. Traumatic brain injury, neuroimaging, and neurodegeneration. Front. Hum. Neurosci., 2013, 7, 395.
[] [PMID: 23964217]
Bramlett, H.M.; Dietrich, W.D. Long-term consequences of traumatic brain injury: current status of potential mechanisms of injury and neurological outcomes. J. Neurotrauma, 2015, 32(23), 1834-1848.
[] [PMID: 25158206]
Ng, S.Y.; Lee, A.Y.W. Traumatic brain injuries: pathophysiology and potential therapeutic targets. Front. Cell. Neurosci., 2019, 13(528), 528.
[] [PMID: 31827423]
Black, K.L.; Hanks, R.A.; Wood, D.L.; Zafonte, R.D.; Cullen, N.; Cifu, D.X.; Englander, J.; Francisco, G.E. Blunt versus penetrating violent traumatic brain injury: frequency and factors associated with secondary conditions and complications. J. Head Trauma Rehabil., 2002, 17(6), 489-496.
[] [PMID: 12802240]
Warden, D. Military TBI during the Iraq and Afghanistan wars. J. Head Trauma Rehabil., 2006, 21(5), 398-402.
[] [PMID: 16983225]
Ling, G.S.F.; Ecklund, J.M. Traumatic brain injury in modern war. Curr. Opin. Anaesthesiol., 2011, 24(2), 124-130.
[] [PMID: 21301332]
Song, H.; Konan, L.M.; Cui, J.; Johnson, C.E.; Langenderfer, M.; Grant, D.; Ndam, T.; Simonyi, A.; White, T.; Demirci, U.; Mott, D.R.; Schwer, D.; Hubler, G.K.; Cernak, I.; DePalma, R.G.; Gu, Z. Ultrastructural brain abnormalities and associated behavioral changes in mice after low-intensity blast exposure. Behav. Brain Res., 2018, 347, 148-157.
[] [PMID: 29526786]
Cernak, I.; Noble-Haeusslein, L.J. Traumatic brain injury: an overview of pathobiology with emphasis on military populations. J. Cereb. Blood Flow Metab., 2010, 30(2), 255-266.
[] [PMID: 19809467]
Risdall, J.E.; Menon, D.K. Traumatic brain injury. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2011, 366(1562), 241-250.
[] [PMID: 21149359]
Cernak, I. Understanding blast-induced neurotrauma: how far have we come? Concussion, 2017, 2(3), CNC42.
[] [PMID: 30202583]
Perez-Garcia, G.; Gama Sosa, M.A.; De Gasperi, R.; Tschiffely, A.E.; McCarron, R.M.; Hof, P.R.; Gandy, S.; Ahlers, S.T.; Elder, G.A. Blast-induced “PTSD”: evidence from an animal model. Neuropharmacology, 2019, 145(Pt B), 220-229.
[] [PMID: 30227150]
Rosenblatt, A.S.; Li, R.; Fortier, C.; Liu, X.; Fonda, J.R.; Villalon, A.; McGlinchey, R.E.; Jorge, R.E. Latent factor structure of PTSD symptoms in veterans with a history of mild traumatic brain injury and close-range blast exposure. Psychol. Trauma, 2019, 11(4), 442-450.
[] [PMID: 30113187]
Narayan, R.K.; Michel, M.E.; Ansell, B.; Baethmann, A.; Biegon, A.; Bracken, M.B.; Bullock, M.R.; Choi, S.C.; Clifton, G.L.; Contant, C.F.; Coplin, W.M.; Dietrich, W.D.; Ghajar, J.; Grady, S.M.; Grossman, R.G.; Hall, E.D.; Heetderks, W.; Hovda, D.A.; Jallo, J.; Katz, R.L.; Knoller, N.; Kochanek, P.M.; Maas, A.I.; Majde, J.; Marion, D.W.; Marmarou, A.; Marshall, L.F.; McIntosh, T.K.; Miller, E.; Mohberg, N.; Muizelaar, J.P.; Pitts, L.H.; Quinn, P.; Riesenfeld, G.; Robertson, C.S.; Strauss, K.I.; Teasdale, G.; Temkin, N.; Tuma, R.; Wade, C.; Walker, M.D.; Weinrich, M.; Whyte, J.; Wilberger, J.; Young, A.B.; Yurkewicz, L. Clinical trials in head injury. J. Neurotrauma, 2002, 19(5), 503-557.
[] [PMID: 12042091]
Machado, S.G.; Murray, G.D.; Teasdale, G.M. Evaluation of designs for clinical trials of neuroprotective agents in head injury. J. Neurotrauma, 1999, 16(12), 1131-1138.
[] [PMID: 10619192]
Higgins, G.C.; Beart, P.M.; Shin, Y.S.; Chen, M.J.; Cheung, N.S.; Nagley, P. Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J. Alzheimers Dis., 2010, 20(Suppl. 2), S453-S473.
[] [PMID: 20463398]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[] [PMID: 16978905]
Tavazzi, B.; Vagnozzi, R.; Signoretti, S.; Amorini, A.M.; Belli, A.; Cimatti, M.; Delfini, R.; Di Pietro, V.; Finocchiaro, A.; Lazzarino, G. Temporal window of metabolic brain vulnerability to concussions: oxidative and nitrosative stresses--part II. Neurosurgery, 2007, 61(2), 390-395.
[] [PMID: 17806141]
Hall, E.D.; Vaishnav, R.A.; Mustafa, A.G. Antioxidant therapies for traumatic brain injury. Neurotherapeutics, 2010, 7(1), 51-61.
[] [PMID: 20129497]
Petronilho, F.; Feier, G.; de Souza, B.; Guglielmi, C.; Constantino, L.S.; Walz, R.; Quevedo, J.; Dal-Pizzol, F. Oxidative stress in brain according to traumatic brain injury intensity. J. Surg. Res., 2010, 164(2), 316-320.
[] [PMID: 19691993]
Bains, M.; Hall, E.D. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim. Biophys. Acta, 2012, 1822(5), 675-684.
[] [PMID: 22080976]
Chen, X.; Guo, C.; Kong, J. Oxidative stress in neurodegenerative diseases. Neural Regen. Res., 2012, 7(5), 376-385.
[] [PMID: 25774178]
Miyamoto, K.; Ohtaki, H.; Dohi, K.; Tsumuraya, T.; Song, D.; Kiriyama, K.; Satoh, K.; Shimizu, A.; Aruga, T.; Shioda, S. Therapeutic time window for edaravone treatment of traumatic brain injury in mice. BioMed Res. Int., 2013, 2013, 379206.
[] [PMID: 23710445]
Wang, G.H.; Jiang, Z.L.; Li, Y.C.; Li, X.; Shi, H.; Gao, Y.Q.; Vosler, P.S.; Chen, J. Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats. J. Neurotrauma, 2011, 28(10), 2123-2134.
[] [PMID: 21732763]
Itoh, T.; Satou, T.; Nishida, S.; Tsubaki, M.; Hashimoto, S.; Ito, H. The novel free radical scavenger, edaravone, increases neural stem cell number around the area of damage following rat traumatic brain injury. Neurotox. Res., 2009, 16(4), 378-389.
[] [PMID: 19590930]
Itoh, T.; Satou, T.; Nishida, S.; Tsubaki, M.; Imano, M.; Hashimoto, S.; Ito, H. Edaravone protects against apoptotic neuronal cell death and improves cerebral function after traumatic brain injury in rats. Neurochem. Res., 2010, 35(2), 348-355.
[] [PMID: 19768539]
Higashi, Y.; Hoshijima, M.; Yawata, T.; Nobumoto, A.; Tsuda, M.; Shimizu, T.; Saito, M.; Ueba, T. Suppression of oxidative stress and 5-lipoxygenase activation by edaravone improves depressive-like behavior after concussion. J. Neurotrauma, 2014, 31(20), 1689-1699.
[] [PMID: 24849726]
Zhang, M.; Teng, C.H.; Wu, F.F.; Ge, L.Y.; Xiao, J.; Zhang, H.Y.; Chen, D.Q. Edaravone attenuates traumatic brain injury through anti-inflammatory and anti-oxidative modulation. Exp. Ther. Med., 2019, 18(1), 467-474.
[] [PMID: 31281440]
Dohi, K.; Satoh, K.; Mihara, Y.; Nakamura, S.; Miyake, Y.; Ohtaki, H.; Nakamachi, T.; Yoshikawa, T.; Shioda, S.; Aruga, T. Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury. J. Neurotrauma, 2006, 23(11), 1591-1599.
[] [PMID: 17115906]
Hosohata, K.; Inada, A.; Oyama, S.; Furushima, D.; Yamada, H.; Iwanaga, K. Surveillance of drugs that most frequently induce acute kidney injury: A pharmacovigilance approach. J. Clin. Pharm. Ther., 2019, 44(1), 49-53.
[] [PMID: 30014591]

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