Abstract
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.
[http://dx.doi.org/10.1161/01.STR.19.4.480] [PMID: 2834836]
[http://dx.doi.org/10.3892/br.2012.7] [PMID: 24648884]
[http://dx.doi.org/10.1161/STROKEAHA.107.181486] [PMID: 17431204]
[http://dx.doi.org/10.3164/jcbn.17-62] [PMID: 29371752]
[http://dx.doi.org/10.2174/157489006775244191] [PMID: 18221078]
[http://dx.doi.org/10.2147/DDDT.S161940] [PMID: 30013324]
[http://dx.doi.org/10.1080/21678421.2017.1353101] [PMID: 28872907]
[http://dx.doi.org/10.1016/j.intimp.2019.105967] [PMID: 31670091]
[http://dx.doi.org/10.1016/j.bioorg.2010.10.003] [PMID: 21078519]
[http://dx.doi.org/10.1517/14656566.2010.493558] [PMID: 20491547]
[http://dx.doi.org/10.1016/j.atherosclerosis.2004.10.037] [PMID: 15721014]
[http://dx.doi.org/10.3164/jcbn.16-63] [PMID: 28163382]
[http://dx.doi.org/10.1517/14656560802636888] [PMID: 19236202]
[http://dx.doi.org/10.1016/j.neuropharm.2004.10.002] [PMID: 15695167]
[http://dx.doi.org/10.1111/j.1527-3466.2008.00041.x] [PMID: 18485133]
[http://dx.doi.org/10.1186/1476-9255-5-7] [PMID: 18507870]
[http://dx.doi.org/10.1038/onc.2008.301] [PMID: 18931691]
[http://dx.doi.org/10.3892/etm.2011.281] [PMID: 22977573]
[http://dx.doi.org/10.1055/s-0038-1649503] [PMID: 29791947]
[http://dx.doi.org/10.3171/foc.2007.22.5.3] [PMID: 17613233]
[http://dx.doi.org/10.1523/JNEUROSCI.4468-06.2007] [PMID: 17267568]
[http://dx.doi.org/10.1016/S1474-4422(19)30078-X] [PMID: 31296369]
[http://dx.doi.org/10.1016/j.pneurobio.2017.10.001] [PMID: 28987927]
[http://dx.doi.org/10.2174/1871527311312050015] [PMID: 23469845]
[http://dx.doi.org/10.1186/2045-8118-11-18] [PMID: 25120903]
[http://dx.doi.org/10.1161/01.STR.0000196957.55928.ab] [PMID: 16339467]
[http://dx.doi.org/10.1161/STROKEAHA.110.592535] [PMID: 20829513]
[http://dx.doi.org/10.1161/01.STR.0000258112.14918.24] [PMID: 17272772]
[http://dx.doi.org/10.1161/01.STR.0000149938.08731.2c] [PMID: 15569863]
[http://dx.doi.org/10.1159/000442715] [PMID: 27051410]
[http://dx.doi.org/10.1111/j.1527-3458.2006.00009.x] [PMID: 16834755]
[http://dx.doi.org/10.1016/j.neulet.2016.08.048] [PMID: 27589890]
[http://dx.doi.org/10.1161/01.STR.0000182241.07096.06] [PMID: 16166574]
[http://dx.doi.org/10.1248/bpb.29.713] [PMID: 16595905]
[http://dx.doi.org/10.1016/j.bbrc.2009.09.015] [PMID: 19737535]
[http://dx.doi.org/10.1161/STROKEAHA.107.486654] [PMID: 18096835]
[http://dx.doi.org/10.1016/j.neures.2007.08.008] [PMID: 17889387]
[http://dx.doi.org/10.1016/j.ejphar.2005.01.050] [PMID: 15840397]
[http://dx.doi.org/10.3999/jscpt.28.693]
[http://dx.doi.org/10.1159/000069318] [PMID: 12715790]
[http://dx.doi.org/10.1016/j.jns.2004.03.002] [PMID: 15178207]
[http://dx.doi.org/10.1016/j.surneu.2005.01.008] [PMID: 16182000]
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.06.001] [PMID: 16198237]
[http://dx.doi.org/10.2176/nmc.46.373] [PMID: 16936457]
[http://dx.doi.org/10.1227/01.NEU.0000338067.83059.EB] [PMID: 19240603]
[http://dx.doi.org/10.1159/000210190] [PMID: 19321945]
[http://dx.doi.org/10.2165/11586550-000000000-00000] [PMID: 20945946]
[http://dx.doi.org/10.1186/1471-2377-11-39] [PMID: 21447190]
[http://dx.doi.org/10.4103/0972-2327.82794] [PMID: 21808471]
[http://dx.doi.org/10.1016/j.jns.2011.09.006] [PMID: 21967833]
[http://dx.doi.org/10.2165/11634290-000000000-00000] [PMID: 22762844]
[http://dx.doi.org/10.1159/000353680] [PMID: 24135530]
[http://dx.doi.org/10.1007/s11845-015-1371-9] [PMID: 26597952]
[http://dx.doi.org/10.1161/STROKEAHA.116.015042] [PMID: 28119434]
[http://dx.doi.org/10.4103/njcp.njcp_367_18] [PMID: 31607719]
[http://dx.doi.org/10.1097/MD.0000000000019316] [PMID: 32080148]
[http://dx.doi.org/10.1161/STROKEAHA.108.520262] [PMID: 19095969]
[http://dx.doi.org/10.1517/13543784.11.11.1623] [PMID: 12437508]
[http://dx.doi.org/10.2176/nmc.ra.2014-0219] [PMID: 25739433]
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.06.016] [PMID: 25307430]
[http://dx.doi.org/10.1371/journal.pone.0098807] [PMID: 24911517]
[http://dx.doi.org/10.1155/2017/6873281] [PMID: 29259732]
[http://dx.doi.org/10.1016/j.jns.2014.07.018] [PMID: 25085762]
[http://dx.doi.org/10.1161/STROKEAHA.118.023815] [PMID: 30741623]
[http://dx.doi.org/10.33552/OJCAM.2019.02.000541]
[http://dx.doi.org/10.1186/1471-2202-9-75] [PMID: 18671880]
[http://dx.doi.org/10.1371/journal.pone.0020677] [PMID: 21677777]
[http://dx.doi.org/10.1016/j.neulet.2019.134438] [PMID: 31422100]
[http://dx.doi.org/10.2176/nmc.48.539] [PMID: 19106491]
[http://dx.doi.org/10.1016/S0022-5223(03)00693-7] [PMID: 14666020]
[http://dx.doi.org/10.1159/000335400] [PMID: 22310070]
[http://dx.doi.org/10.1016/j.athoracsur.2004.02.133] [PMID: 15276530]
[http://dx.doi.org/10.1097/01.brs.0000162402.79482.fd] [PMID: 15897829]
[http://dx.doi.org/10.4103/1673-5374.141808] [PMID: 25374594]
[http://dx.doi.org/10.4103/1673-5374.152376] [PMID: 25883621]
[http://dx.doi.org/10.4103/am.am_48_19]
[http://dx.doi.org/10.15585/mmwr.mm6707a3] [PMID: 29470458]
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.11.018] [PMID: 19969067]
[http://dx.doi.org/10.1007/s12035-015-9567-6] [PMID: 26666663]
[http://dx.doi.org/10.1007/s10072-019-04055-3] [PMID: 31471712]
[PMID: 29290672]
[http://dx.doi.org/10.1056/NEJM199403033300901] [PMID: 8302340]
[http://dx.doi.org/10.1080/14737175.2019.1581610] [PMID: 30810406]
[http://dx.doi.org/10.1371/journal.pone.0140316] [PMID: 26469273]
[http://dx.doi.org/10.1016/j.brainres.2011.01.058] [PMID: 21276427]
[http://dx.doi.org/10.1016/j.expneurol.2008.07.017] [PMID: 18718468]
[http://dx.doi.org/10.1016/S0006-8993(97)00490-3] [PMID: 9262182]
[http://dx.doi.org/10.1002/med.21528] [PMID: 30101496]
[http://dx.doi.org/10.1080/14656566.2017.1319937] [PMID: 28406335]
[http://dx.doi.org/10.1016/S0022-510X(99)00210-5] [PMID: 10540002]
[http://dx.doi.org/10.17925/USN.2018.14.1.47]
[http://dx.doi.org/10.1080/17482960600881870] [PMID: 17127563]
[http://dx.doi.org/10.3109/21678421.2014.959024] [PMID: 25286015]
[http://dx.doi.org/10.1016/S1474-4422(17)30115-1] [PMID: 28522181]
[http://dx.doi.org/10.1080/21678421.2017.1363780] [PMID: 28872917]
[http://dx.doi.org/10.3109/17482960903093710] [PMID: 19634063]
[http://dx.doi.org/10.1080/21678421.2017.1364269] [PMID: 28872920]
[http://dx.doi.org/10.1002/mus.26740] [PMID: 31621933]
[http://dx.doi.org/10.1038/nrd3681] [PMID: 22378269]
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[http://dx.doi.org/10.1038/nrd2961] [PMID: 19949401]
[http://dx.doi.org/10.1038/534314a] [PMID: 27306171]
[http://dx.doi.org/10.1016/j.neuropharm.2018.04.006] [PMID: 29630902]
[http://dx.doi.org/10.1089/neu.2018.5778] [PMID: 29756522]
[http://dx.doi.org/10.1002/ana.24897] [PMID: 28198092]
[http://dx.doi.org/10.1089/neu.2004.21.1168] [PMID: 15453987]
[http://dx.doi.org/10.1161/STROKEAHA.113.002813] [PMID: 24072001]
[http://dx.doi.org/10.1186/s12868-014-0125-3] [PMID: 25416145]
[http://dx.doi.org/10.1002/jnr.22722] [PMID: 21812016]
[http://dx.doi.org/10.1038/srep45780] [PMID: 28387380]
[http://dx.doi.org/10.1016/j.nic.2010.08.001] [PMID: 20974375]
[http://dx.doi.org/10.1089/neu.2008.0586] [PMID: 18627252]
[http://dx.doi.org/10.3389/fnhum.2013.00395] [PMID: 23964217]
[http://dx.doi.org/10.1089/neu.2014.3352] [PMID: 25158206]
[http://dx.doi.org/10.3389/fncel.2019.00528] [PMID: 31827423]
[http://dx.doi.org/10.1097/00001199-200212000-00001] [PMID: 12802240]
[http://dx.doi.org/10.1097/00001199-200609000-00004] [PMID: 16983225]
[http://dx.doi.org/10.1097/ACO.0b013e32834458da] [PMID: 21301332]
[http://dx.doi.org/10.1016/j.bbr.2018.03.007] [PMID: 29526786]
[http://dx.doi.org/10.1038/jcbfm.2009.203] [PMID: 19809467]
[http://dx.doi.org/10.1098/rstb.2010.0230] [PMID: 21149359]
[http://dx.doi.org/10.2217/cnc-2017-0006] [PMID: 30202583]
[http://dx.doi.org/10.1016/j.neuropharm.2018.09.023] [PMID: 30227150]
[http://dx.doi.org/10.1037/tra0000399] [PMID: 30113187]
[http://dx.doi.org/10.1089/089771502753754037] [PMID: 12042091]
[http://dx.doi.org/10.1089/neu.1999.16.1131] [PMID: 10619192]
[http://dx.doi.org/10.3233/JAD-2010-100321] [PMID: 20463398]
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[http://dx.doi.org/10.1227/01.NEU.0000255525.34956.3F] [PMID: 17806141]
[http://dx.doi.org/10.1016/j.nurt.2009.10.021] [PMID: 20129497]
[http://dx.doi.org/10.1016/j.jss.2009.04.031] [PMID: 19691993]
[http://dx.doi.org/10.1016/j.bbadis.2011.10.017] [PMID: 22080976]
[http://dx.doi.org/10.3969/j.issn.1673-5374.2012.05.009] [PMID: 25774178]
[http://dx.doi.org/10.1155/2013/379206] [PMID: 23710445]
[http://dx.doi.org/10.1089/neu.2011.1939] [PMID: 21732763]
[http://dx.doi.org/10.1007/s12640-009-9081-6] [PMID: 19590930]
[http://dx.doi.org/10.1007/s11064-009-0061-2] [PMID: 19768539]
[http://dx.doi.org/10.1089/neu.2014.3331] [PMID: 24849726]
[http://dx.doi.org/10.3892/etm.2019.7632] [PMID: 31281440]
[http://dx.doi.org/10.1089/neu.2006.23.1591] [PMID: 17115906]
[http://dx.doi.org/10.1111/jcpt.12748] [PMID: 30014591]