Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Fluvoxamine and Amantadine: Central Nervous System Acting Drugs Repositioned for COVID-19 as Early Intervention

Author(s): Konrad Rejdak and Paweł Grieb*

Volume 20, Issue 4, 2022

Published on: 28 December, 2021

Page: [777 - 781] Pages: 5

DOI: 10.2174/1570159X19666210729123734

open access plus

Abstract

Background: As the World faces unprecedented pandemic caused by SARS-CoV-2 virus, repositioning of existing drugs to treatment of COVID-19 disease is urgently awaited, provided that high quality scientific evidence supporting safety and efficacy in this new indication is gathered. Efforts concerning drugs repositioning to COVID-19 were mostly focused on antiviral drugs, or drugs targeting the late phase of the disease.

Methods: Based on published research, the pharmacological activities of fluvoxamine and amantadine, two well-known drugs widely used in clinical practice for psychiatric and neurological diseases, respectively, have been reviewed, with a focus on their potential therapeutic importance in the treatment of COVID-19.

Results: Several preclinical and clinical reports were identified suggesting that these two drugs might exert protective effects in the early phases of COVID-19.

Conclusion: Preclinical and early clinical evidence are presented indicating that these drugs hold promise to prevent COVID-19 progression when administered early during the course of infection.

Keywords: Drug repositioning, SARS-CoV-2, COVID-19, treatment, amantadine, fluvoxamine.

Graphical Abstract
[1]
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.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[2]
Wouters, O.J.; McKee, M.; Luyten, J. Estimated research and development investment needed to bring a new medicine to market, 2009-2018. JAMA, 2020, 323(9), 844-853.
[http://dx.doi.org/10.1001/jama.2020.1166] [PMID: 32125404]
[3]
Oprea, T.I.; Overington, J.P. Computational and practical aspects of drug repositioning. Assay Drug Dev. Technol., 2015, 13(6), 299-306.
[http://dx.doi.org/10.1089/adt.2015.29011.tiodrrr] [PMID: 26241209]
[4]
Jamalipour, S.G.; Iravani, S. Potential inhibitors of SARS-CoV-2: Recent advances. J. Drug Target., 2020, 3, 1-16.
[5]
Payandeh, Z. The immunology of SARS-CoV-2 infection, the potential antibody based treatments and vaccination strategies. Expert Rev. Anti Infect. Ther., 2020, 30, 1-13.
[PMID: 33307883]
[6]
Saxena, A. Drug targets for COVID-19 therapeutics: Ongoing global efforts. J. Biosci., 2020, 45, 87.
[http://dx.doi.org/10.1007/s12038-020-00067-w] [PMID: 32661214]
[7]
Ungogo, M.A.; Mohammed, M.; Umar, B.N.; Bala, A.A.; Khalid, G.M. Review of pharmacologic and immunologic agents in the management of COVID-19. Health, 2021, 3(3), 148-155.
[http://dx.doi.org/10.1016/j.bsheal.2021.01.001] [PMID: 33458647]
[8]
Benfield, P.; Ward, A. Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs, 1986, 32(4), 313-334.
[http://dx.doi.org/10.2165/00003495-198632040-00002] [PMID: 3096686]
[9]
Hashimoto, K. Repurposing of CNS drugs to treat COVID-19 infection: Targeting the sigma-1 receptor. Eur. Arch. Psychiatry Clin. Neurosci., 2021, 271(2), 249-258.
[http://dx.doi.org/10.1007/s00406-020-01231-x] [PMID: 33403480]
[10]
Weissman, A.D.; Su, T.P.; Hedreen, J.C.; London, E.D. Sigma receptors in post-mortem human brains. J. Pharmacol. Exp. Ther., 1988, 247(1), 29-33.
[PMID: 2845055]
[11]
Collier, T.L.; Waterhouse, R.N.; Kassiou, M. Imaging sigma receptors: Applications in drug development. Curr. Pharm. Des., 2007, 13(1), 51-72.
[http://dx.doi.org/10.2174/138161207779313740] [PMID: 17266588]
[12]
Grootjans, J.; Kaser, A.; Kaufman, R.J.; Blumberg, R.S. The unfolded protein response in immunity and inflammation. Nat. Rev. Immunol., 2016, 16(8), 469-484.
[http://dx.doi.org/10.1038/nri.2016.62] [PMID: 27346803]
[13]
Rosen, D.A.; Seki, S.M.; Fernández-Castañeda, A.; Beiter, R.M.; Eccles, J.D.; Woodfolk, J.A.; Gaultier, A. Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci. Transl. Med., 2019, 11(478) ,eaau5266.
[http://dx.doi.org/10.1126/scitranslmed.aau5266] [PMID: 30728287]
[14]
Santerre, M.; Arjona, S.P.; Allen, C.N.; Shcherbik, N.; Sawaya, B.E. Why do SARS-CoV-2 NSPs rush to the ER? J. Neurol., 2020, 1, 1-10.
[http://dx.doi.org/10.1007/s00415-020-10197-8] [PMID: 32870373]
[15]
So, J.S. Roles of endoplasmic reticulum stress in immune responses. Mol. Cells, 2018, 41(8), 705-716.
[PMID: 30078231]
[16]
16Grieb, P.; Swiatkiewicz, M.; Prus, K.; Rejdak, K. Hypoxia may be a determinative factor in COVID-19 progression.,
[17]
Akman, M.; Belisario, D.C.; Salaroglio, I.C.; Kopecka, J.; Donadelli, M.; De Smaele, E.; Riganti, C. Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons. J. Exp. Clin. Cancer Res., 2021, 40(1), 28.
[http://dx.doi.org/10.1186/s13046-020-01824-3] [PMID: 33423689]
[18]
Lenze, E.J.; Mattar, C.; Zorumski, C.F.; Stevens, A.; Schweiger, J.; Nicol, G.E.; Miller, J.P.; Yang, L.; Yingling, M.; Avidan, M.S.; Reiersen, A.M. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial. JAMA, 2020, 324(22), 2292-2300.
[http://dx.doi.org/10.1001/jama.2020.22760] [PMID: 33180097]
[19]
Sakaguchi, T.; Leser, G.P.; Lamb, R.A. The ion channel activity of the influenza virus M2 protein affects transport through the Golgi apparatus. J. Cell Biol., 1996, 133(4), 733-747.
[http://dx.doi.org/10.1083/jcb.133.4.733] [PMID: 8666660]
[20]
Lampejo, T. Influenza and antiviral resistance: An overview. Eur. J. Clin. Microbiol. Infect. Dis., 2020, 39(7), 1201-1208.
[http://dx.doi.org/10.1007/s10096-020-03840-9] [PMID: 32056049]
[21]
Hesselink, J.M.K. Amantadine and phenytoin: patent protected cases of drug repositioning. Clin. Investig. (Lond.), 2017, 7, 11-16.
[22]
Dey, D.; Siddiqui, S.I.; Mamidi, P.; Ghosh, S.; Kumar, C.S.; Chattopadhyay, S.; Ghosh, S.; Banerjee, M. The effect of amantadine on an ion channel protein from Chikungunya virus. PLoS Negl. Trop. Dis., 2019, 13(7) ,e0007548.
[http://dx.doi.org/10.1371/journal.pntd.0007548] [PMID: 31339886]
[23]
Carreño, V. Review article: management of chronic hepatitis C in patients with contraindications to anti-viral therapy. Aliment. Pharmacol. Ther., 2014, 39(2), 148-162.
[http://dx.doi.org/10.1111/apt.12562] [PMID: 24279580]
[24]
Xing, W.; Huang, P.; Lu, Y.; Zeng, W.; Zuo, Z. Amantadine attenuates sepsis-induced cognitive dysfunction possibly not through inhibiting toll-like receptor 2. J. Mol. Med. (Berl.), 2018, 96(5), 391-402.
[http://dx.doi.org/10.1007/s00109-018-1631-z] [PMID: 29502203]
[25]
Nakano, T.; Hasegawa, T.; Suzuki, D.; Motomura, E.; Okada, M. Amantadine combines astroglial system Xc- activation with glutamate/NMDA receptor inhibition. Biomolecules, 2019, 9(5), 191.
[http://dx.doi.org/10.3390/biom9050191] [PMID: 31108896]
[26]
Müller, T.; Kuhn, W.; Möhr, J.D. Evaluating ADS5102 (amantadine) for the treatment of Parkinson’s disease patients with dyskinesia. Expert Opin. Pharmacother., 2019, 20(10), 1181-1187.
[http://dx.doi.org/10.1080/14656566.2019.1612365] [PMID: 31058557]
[27]
Ormstad, H.; Simonsen, C.S.; Broch, L.; Maes, D.M.; Anderson, G.; Celius, E.G. Chronic fatigue and depression due to multiple sclerosis: Immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways. Mult. Scler. Relat. Disord., 2020, 46 ,102533.
[http://dx.doi.org/10.1016/j.msard.2020.102533] [PMID: 33010585]
[28]
Ma, H.M.; Zafonte, R.D. Amantadine and memantine: A comprehensive review for acquired brain injury. Brain Inj., 2020, 34(3), 299-315.
[http://dx.doi.org/10.1080/02699052.2020.1723697] [PMID: 32078407]
[29]
Cimolai, N. Potentially repurposing adamantanes for COVID-19. J. Med. Virol., 2020, 92(6), 531-532.
[http://dx.doi.org/10.1002/jmv.25752] [PMID: 32176361]
[30]
Tipton, P.W.; Wszolek, Z.K. What can Parkinson’s disease teach us about COVID-19? Neurol. Neurochir. Pol., 2020, 54(2), 204-206.
[PMID: 32323862]
[31]
Abreu, G.E.A.; Aguilar, M.E.H.; Covarrubias, D.H.; Durán, F.R. Amantadine as a drug to mitigate the effects of COVID-19. Med. Hypotheses, 2020, 140 ,109755.
[http://dx.doi.org/10.1016/j.mehy.2020.109755] [PMID: 32361100]
[32]
Smieszek, S.P.; Przychodzen, B.P.; Polymeropoulos, M.H. Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment. Int. J. Antimicrob. Agents, 2020, 55(6) ,106004.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106004] [PMID: 32361028]
[33]
Rejdak, K.; Grieb, P. Adamantanes might be protective from COVID-19 in patients with neurological diseases: multiple sclerosis, parkinsonism and cognitive impairment. Mult. Scler. Relat. Disord., 2020, 42 ,102163.
[http://dx.doi.org/10.1016/j.msard.2020.102163] [PMID: 32388458]
[34]
Yu, Y.; Travaglio, M.; Popovic, R.; Leal, N.S.; Martins, L.M. Alzheimer’s and parkinson’s diseases predict different COVID-19 outcomes: A UK biobank study. Geriatrics (Basel), 2021, 6(1), 10.
[http://dx.doi.org/10.3390/geriatrics6010010] [PMID: 33530357]
[35]
Aranda-Abreu, G.E.; Aranda-Martínez, J.D.; Araújo, R.; Hernández-Aguilar, M.E.; Herrera-Covarrubias, D.; Rojas-Durán, F. Observational study of people infected with SARS-Cov-2, treated with amantadine. Pharmacol. Rep., 2020, 72(6), 1538-1541.
[http://dx.doi.org/10.1007/s43440-020-00168-1] [PMID: 33040252]
[36]
Araújo, R.; Aranda-Martínez, J.D.; Aranda-Abreu, G.E. Amantadine treatment for people with COVID-19. Arch. Med. Res., 2020, 51(7), 739-740.
[http://dx.doi.org/10.1016/j.arcmed.2020.06.009] [PMID: 32571606]
[37]
Mandala, V.S.; McKay, M.J.; Shcherbakov, A.A.; Dregni, A.J.; Kolocouris, A.; Hong, M. Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers. Nat. Struct. Mol. Biol., 2020, 27(12), 1202-1208.
[http://dx.doi.org/10.1038/s41594-020-00536-8] [PMID: 33177698]
[38]
Baig, A.M.; Khaleeq, A.; Syeda, H. Docking prediction of amantadine in the receptor binding domain of spike protein of SARS-CoV-2. ACS Pharmacol. Transl. Sci., 2020, 3(6), 1430-1433.
[http://dx.doi.org/10.1021/acsptsci.0c00172] [PMID: 33344913]
[39]
Kim, P.S.; Read, S.W.; Fauci, A.S. Therapy for early COVID-19: a critical need. JAMA, 2020, 324(21), 2149-2150.
[http://dx.doi.org/10.1001/jama.2020.22813] [PMID: 33175121]
[40]
Danysz, W.; Dekundy, A.; Scheschonka, A.; Riederer, P. Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials. J. Neural Transm. (Vienna), 2021, 128(2), 127-169.
[http://dx.doi.org/10.1007/s00702-021-02306-2] [PMID: 33624170]
[41]
Luyten, J.; McKee, M.; Wouters, O.J. How much does research and development of a drug cost? A call for more transparency. Ned. Tijdschr. Geneeskd., 2020, 164, D5018.
[PMID: 32940989]
[42]
42Clinical Trials Arena Eli Lilly’s monoclonal antibody bamlanivimab value allows payer grace for Covid-19. 2020. Available from:clinicaltrialsarena.com 18 November 2020.
[43]
Ayres, J.S. Surviving COVID-19: A disease tolerance perspective. Sci. Adv., 2020, 6 ,eabc1518.

© 2024 Bentham Science Publishers | Privacy Policy