Combination Of Riluzole And Rivastigmine- A Potential Treatment Strategy For Alzheimer’s Disease

Main Article Content

Chintha Narendar
M Tharani
Gaddam Narasimha Rao
M Anvesh Raj
Antony Justin

Keywords

Alzheimer’s disease, Riluzole, Rivastigmine, Combination therapy, neurodegenerative disease

Abstract

To fulfill clinical needs, it is essential to deploy viable treatment techniques for Alzheimer's disease (AD). The development of potential therapeutic drugs for the treatment of Alzheimer's disease in the early stages and the optimization of symptomatic treatment are top priorities in AD research. Recently multitarget therapies are gaining a lot of interest due to their potential advantages. The current review aims to review the advantages of combined targeting of Cholinesterase inhibitors (ChEIs) and Nmethyl D-aspartate (NMDA) antagonists in the treatment of AD. In order to evaluate the all-possible aspects of ChEIs and NMDA antagonists in the treatment of AD, we have examined documentation available in published literature. Recently, Riluzole has been approved for amyotrophic lateral
sclerosis (ALS), and rivastigmine for Alzheimer's disease. A recent study suggested that Riluzole may show therapeutic benefits in the treatment of AD. As, Rivastigmine is an existing therapy for mild to moderate AD, drugs that act for severe AD are necessary. So, combination therapy (CT) with Riluzole and rivastigmine may act as a potential treatment strategy for AD is beneficial. When compared with monotherapy, the combination approach simplifies the treatment regimen and increases patient compliance. For sufferers with excessive AD, CT with ChEIs and NMDA antagonists seems to be the simplest and most powerful therapy.

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References

1. Plamena R. Angelova,Andrey Y. Abramov. Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Letters. 2018; 592(5):692-702. doi:10.1002/1873-3468.12964.
2. Daniel M Skovronsky, Virginia M-Y Lee, John Q Trojanowski. Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol. 2006; 1:151-70. DOI: 10.1146/annurev.pathol.1.110304.100113, PMID: 18039111.
3. Paolo Stanzione, Domenicantonio Tropepi. Drugs and clinical trials in neurodegenerative diseases. Ann Ist Super Sanita 2011;47(1):49-54.
DOI: 10.4415/ANN_11_01_11, PMID: 21430339.
4. Bogousslavsky J, Boller F, Iwata M, editors. A History of Neuropsychology. Front Neurol Neurosci. Basel: Karger; 2019.
5. Lipowski Z.J. Psychosomatic Medicine and Liaison Psychiatry. Springer: New York, NY; 1984.
6. Jibson Michael, Seyfried Lisa. DSM-5 Teaching Materials: A Critical Review. Academic Psychiatry. 2016; 41. 10.1007/s40596-016-0614-z.
7. Alzheimer’s Association. Alzheimer’s disease Facts and Figures. Alzheimer’s Dement 2016 Apr;12(4):459-509. DOI: 10.1016/j.jalz.2016.03.001,
PMID: 27570871.
8. Robert H Brown, Ammar Al-Chalabi. Amyotrophic Lateral Sclerosis. N Engl J Med 2017 Jul 13;377(2):162-172. doi: 10.1056/NEJMra1603471, PMID: 28700839.
9. Narwat A, Sharma V, Kumar S, Rani S. Recent advances in pharmacotherapy of alzheimer’s disease. Int j curr pharm res. 2021;13(6):20-3.
Doi: https://dx.doi.org/10.22159/ijcpr.2021v13i6.
10. Domenico Praticò. Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. Trends Pharmacol Sci. 2008 Dec;29(12):609-15. doi:
10.1016/j.tips.2008.09.001, PMID: 18838179.
11. Swetha G, Anjali R, Saniya Tabassum Dz. Oxidative stress in alzheimer’s disease–evaluating the amyloid beta hypothesis. Int j curr
pharm res. 2021;13(5):32-8. Doi: https://dx.doi.org/10.22159/ijcpr.2021v13i5.
12. Antonio Federico, Elena Cardaioli, Paola Da Pozzo, Patrizia Formichi, Gian Nicola Gallus, Elena Radi. Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci. 2012 Nov 15;322(1-2):254-62. doi: 10.1016/j.jns.2012.05.030, PMID: 22669122.
13. M L Crismon . Tacrine: first drug approved for Alzheimer's disease. Ann Pharmacother. 1994 Jun;28(6):744-51. doi: 10.1177/106002809402800612, PMID: 7919566.
14. Agneta Nordberg , Clive Ballard, Roger Bullock, Taher Darreh-Shori, Monique Somogyi. A review of butyrylcholinesterase as a therapeutic
target in the treatment of Alzheimer's disease. Prim Care Companion CNS Disord. 2013;15(2):PCC.12r01412. doi: 10.4088/PCC.12r01412, PMID: 23930233.
15. E L Conway. A review of the randomized controlled trials of tacrine in the treatment of Alzheimer's disease: methodologic considerations. Clin Neuropharmacol. 1998 JanFeb;21(1):8-17. PMID: 9579280.
16. N Qizilbash, A Whitehead, J Higgins, G Wilcock, L Schneider, M Farlow. Cholinesterase inhibition for Alzheimer disease: a meta-analysis
of the tacrine trials. Dementia Trialists' Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. doi: 10.1001/jama.280.20.1777, PMID: 9842955.
17. M Farlow , S I Gracon, L A Hershey, K W Lewis, C H Sadowsky, J Dolan-Ureno. A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group. JAMA. 1992 Nov 11;268(18):2523-9. PMID: 1404819.
18. Jennifer Y Y Szeto, Simon J G Lewis. Current Treatment Options for Alzheimer's Disease and Parkinson's Disease Dementia. Curr Neuropharmacol. 2016;14(4):326-38. doi: 10.2174/1570159x14666151208112754, PMID: 26644155.
19. Alireza Atri. Current and Future Treatments in Alzheimer's Disease. Semin Neurol. 2019 Apr;39(2):227-240. doi: 10.1055/s-0039-1678581, PMID: 30925615.
20. Joanne Knowles. Donepezil in Alzheimer's disease: an evidence-based review of its impact on clinical and economic outcomes. Core Evid.
2006;1(3):195-219. PMID: 22500154.
21. Atsushi Tanaka, Shoichi Koga, Yoshihiro Hiramatsu. Donepezil-induced adverse side effects of cardiac rhythm: 2 cases report of
atrioventricular block and Torsade de Pointes. Intern Med. 2009;48(14):1219-23. doi: 10.2169/internalmedicine.48.2181, PMID: 19602789.
22. Weinstock, M. Selectivity of Cholinesterase Inhibition. Mol Diag Ther. 1999; 12, 307–323 https://doi.org/10.2165/00023210-199912040-
00005.
23. Michael Shanks, Miia Kivipelto, Roger Bullock, Roger Lane. Cholinesterase inhibition: is there evidence for disease-modifying effects?.
Curr Med Res Opin. 2009 Oct;25(10):2439-46. doi: 10.1185/03007990903209332, PMID: 19678754.
24. Steven Ferris, Agneta Nordberg, Hilkka Soininen, Taher Darreh-Shori, Roger Lane. Progression from mild cognitive impairment to Alzheimer's disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment. Pharmacogenet Genomics. 2009 Aug;19(8):635-46. doi: 10.1097/FPC.0b013e32832f8c17, PMID: 19617863.
25. Marwan N Sabbagh, Martin R Farlow, Normal Relkin, Thomas G Beach. Do cholinergic therapies have disease-modifying effects in Alzheimer's disease?. Alzheimers Dement. 2006 Apr;2(2):118-25. doi: 10.1016/j.jalz.2006.02.001, PMID: 19595868.
26. Thibault B Ali, Thomas R Schleret, Brian M Reilly, Winston Yuchen Chen, Ruben Abagyan. Adverse Effects of Cholinesterase Inhibitors in
Dementia, According to the Pharmacovigilance Databases of the United-States and Canada. PLoS One. 2015 Dec 7;10(12):e0144337. doi:
10.1371/journal.pone.0144337, PMID: 26642212.
27. Hermann Am Mucke.. The case of galantamine: repurposing and late blooming of a cholinergic drug. Future Sci OA. 2015 Sep 3;1(4):FSO73.
doi: 10.4155/fso.15.73, PMID: 28031923.
28. Natalia M Kowal, Philip K Ahring, Vivian W Y Liao, Dinesh C Indurti, Benjamin S Harvey, Susan M O'Connor, Mary Chebib, Elin S
Olafsdottir, Thomas Balle. Galantamine is not a positive allosteric modulator of human α4β2 or α7 nicotinic acetylcholine receptors. Br J Pharmacol. 2018 Jul;175(14):2911-2925. doi: 10.1111/bph.14329, PMID: 29669164.
29. E N Popova, N N Bogolepov. Changes in neurons of certain regions of the brain under the influence of nivaline. Bull Exp Biol Med. 1965;59:572–577.
30. D S Woodruff-Pak, R W Vogel 3rd, G L Wenk. Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. doi: 10.1073/pnas.98.4.2089, PMID: 11172080.
31. Olin JT, Schneider L. Galantamine for Alzheimer's disease. Cochrane Database of Systematic Reviews. 2002; 3: CD001747. DOI:
10.1002/14651858.CD001747.
32. Sean Lilienfeld. CNS Drug Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with
Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. doi: 10.1111/j.1527-3458.2002.tb00221.x, PMID: 12177686.
33. Sandra I Mota, Ildete L Ferreira, A Cristina Rego. Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors. Neuropharmacology. 2014 Jan;76 Pt A:16-26. doi: 10.1016/j.neuropharm.2013.08.013, PMID: 23973316.
34. S M Rothman, J W Olney. Glutamate and the pathophysiology of hypoxic--ischemic brain damage. Ann Neurol. 1986 Feb;19(2):105-11. doi: 10.1002/ana.410190202, PMID: 2421636.
35. D W Choi. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988 Oct;1(8):623-34. doi: 10.1016/0896-6273(88)90162-6, PMID: 2908446.
36. D W Choi. Excitotoxic cell death. J Neurobiol. 1992 Nov;23(9):1261-76. doi: 10.1002/neu.480230915, PMID: 1361523.
37. Erin J Kodis, Sophie Choi, Eric Swanson, Gonzalo Ferreira, George S Bloom. Nmethyl-D-aspartate receptor-mediated calcium influx connects amyloid-β oligomers to ectopic neuronal cell cycle reentry in Alzheimer's disease. Alzheimers Dement. 2018 Oct;14(10):1302-1312. doi: 10.1016/j.jalz.2018.05.017, PMID: 30293574.
38. Rui Wang, P Hemachandra Reddy. Role of Glutamate and NMDA Receptors in Alzheimer's Disease. J Alzheimers Dis. 2017;57(4):1041-1048. doi: 10.3233/JAD-160763, PMID: 27662322.
39. Chris Fox, Monica Crugel, Ian Maidment, Bjorn Henrik Auestad, Simon Coulton, Adrian Treloar, Clive Ballard, Malaz Boustani, Cornelius Katona, Gill Livingston.Efficacy of memantine for agitation in Alzheimer's dementia: a randomised doubleblind placebo controlled trial. PLoS
One. 2012;7(5):e35185. doi: 10.1371/journal.pone.0035185, PMID: 22567095.
40. David Wilkinson, Nick C Fox, Frederik Barkhof, Ravinder Phul, Ole Lemming, Philip Scheltens. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial. J Alzheimers Dis. 2012;29(2):459-69. doi: 10.3233/JAD-2011-111616, PMID: 22269160.
41. S Bakchine, H Loft. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind,
placebo-controlled 6-month study. J Alzheimers Dis. 2007 Jul;11(4):471-9. doi: 10.3233/jad2007-11409, PMID: 17656827.
42. Matthew Smith, Jennie Wells, Michael Borrie. Treatment effect size of memantine therapy in Alzheimer disease and vascular dementia.
Alzheimer Dis Assoc Disord. 2006 JulSep;20(3):133-7. doi: 10.1097/00002093-200607000-00002, PMID: 16917181.
43. Stuart A Lipton. Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and Snitrosylation. Curr Drug Targets. 2007 May;8(5):621-32. doi: 10.2174/138945007780618472, PMID: 17504105.
44. Catherine E Creeley, David F Wozniak, Anthony Nardi, Nuri B Farber, John W Olney. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain. Neurobiol Aging. 2008 Feb;29(2):153-67. doi: 10.1016/j.neurobiolaging.2006.10.020, PMID: 17112636.
45. Alireza Atri, Lynn W Shaughnessy, Joseph J Locascio, John H Growdon. Long-term course and effectiveness of combination therapy in
Alzheimer disease. Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):209-21. doi: 10.1097/WAD.0b013e31816653bc, PMID: 18580597.
46. G Giaccone, B Pedrotti, A Migheli, L Verga, J Perez, G Racagni, M A Smith, G Perry, L De Gioia, C Selvaggini, M Salmona, J Ghiso, B
Frangione, K Islam, O Bugiani, F Tagliavini. A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease. Am J Pathol. 1996 Jan;148(1):79-87. PMCID: PMC1861592.
47. J P Hubert, A Doble. Ibotenic acid stimulates D-[3H]aspartate release from cultured cerebellar granule cells. Neurosci Lett. 1989 Jan
30;96(3):345-50. doi: 10.1016/0304-3940(89)90403-5, PMID: 2541382.
48. L. Barbeito, A. Chéramy, G. Godeheu, J. M. Desce, J. Glowinski. Glutamate Receptors of a Quisqualate-Kainate Subtype are Involved in the
Presynaptic Regulation of Dopamine Release in the Cat Caudate Nucleus in vivo. Eur J Neurosci. 1990;2(4):304-311. doi: 10.1111/j.1460-9568.1990.tb00422.x, PMID: 12106037.
49. Anand R, Gharabawi G. Clinical development of Exelon (ENA 713): the ADENA programme. J Drug Dev Clin Pract 1996;8:9-16. WOS:A1996VJ32200007.
50. Enz A, Floersheim P. Cholinesterase inhibitors: an overview of their mechanism of action. In: Giacobini E, Becker R, editors. Alzheimer’s
disease. Therapeutic strategies. Boston: Birkhauser, 1994,211–15.
51. Aline Milane, Christine Fernandez, Sarah Vautier, Gilbert Bensimon, Vincent Meininger, Robert Farinotti. Minocycline and riluzole brain disposition: interactions with pglycoprotein at the blood-brain barrier. J Neurochem. 2007 Oct;103(1):164-73. doi: 10.1111/j.1471-4159.2007.04772.x, PMID: 17635670.
52. Loqman A Mohamed, Shashirekha Markandaiah, Silvia Bonanno, Piera Pasinelli, Davide Trotti. Blood-Brain Barrier Driven Pharmacoresistance in Amyotrophic Lateral Sclerosis and Challenges for Effective Drug Therapies. AAPS J. 2017 Nov;19(6):1600-1614. doi: 10.1208/s12248-017-0120-6, PMID: 28779378.
53. Md Tanvir Kabir, Md Sahab Uddin, Abdullah Al Mamun, Philippe Jeandet, Lotfi Aleya, Rasha A Mansouri, Ghulam Md Ashraf, Bijo
Mathew, May N Bin-Jumah, Mohamed M AbdelDaim. Combination Drug Therapy for the Management of Alzheimer's Disease. Int J Mol
Sci. 2020 May 5;21(9):3272. doi: 10.3390/ijms21093272, PMID: 32380758.
54. Beate Schmitt 1, Tanja Bernhardt, Hans-Juergen Moeller, Isabella Heuser, Lutz Frölich. Combination therapy in Alzheimer's disease: a
review of current evidence. CNS Drugs. 2004;18(13):827-44. doi: 10.2165/00023210-200418130-00001, PMID: 15521788.
55. Vivian W Chow 1, Alena V Savonenko, Tatiana Melnikova, Hyunsu Kim, Donald L Price, Tong Li, Philip C Wong. Modeling an anti-amyloid
combination therapy for Alzheimer's disease. Sci Transl Med. 2010 Jan 6;2(13):13ra1. doi: 10.1126/scitranslmed.3000337, PMID: 20371462.
56. Ralf Ihl 1, Robertas Bunevicius, Lutz Frölich, Bengt Winblad, Lon S Schneider, Bruno Dubois, Alistair Burns, Florence Thibaut, Siegfried
Kasper, Hans-Jürgen Möller, WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Dementia. WFSBP Task Force on
Treatment Guidelines for Alzheimer's Disease and other Dementias. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer's disease and other dementias. Int J Psychiatry Clin Pract. 2015 Mar;19(1):2-7. doi: 10.3109/13651501.2014.961931, PMID: 25195764.
57. Jeffrey L Cummings. Treatment of Alzheimer's disease: the role of symptomatic agents in an era of disease-modifying therapies. Rev Neurol Dis. 2007 Spring;4(2):57-62. PMID: 17609636.
58. Martin R Farlow, Michael L Miller, Vojislav Pejovic. Treatment options in Alzheimer's disease: maximizing benefit, managingexpectations. Dement Geriatr Cogn Disord. 2008;25(5):408-22. doi: 10.1159/000122962, PMID: 18391487.
59. Seong Hye Choi, Kyung Won Park, Duk L Na, Hyun Jeong Han, Eun-Joo Kim, Yong S Shim, Jae-Hong Lee. Tolerability and efficacy of
memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer's disease: a multicenter, randomized,
open-label, parallel-group study. Curr Med Res Opin. 2011 Jul;27(7):1375-83. doi: 10.1185/03007995.2011.582484, PMID: 21561398.
60. Martin R Farlow, Gus Alva, Xiangyi Meng, Jason T Olin. A 25-week, open-label trial investigating rivastigmine transdermal patches
with concomitant memantine in mild-to-moderate Alzheimer's disease: a post hoc analysis. Curr Med Res Opin. 2010 Feb;26(2):263-9. doi:
10.1185/03007990903434914, PMID: 19929593.
61. Stuart J Thomas, George T Grossberg. Memantine: a review of studies into its safety and efficacy in treating Alzheimer’s disease and other
dementias. Clin Interv Aging. 2009;4:367-77. doi: 10.2147/cia.s6666, PMID: 19851512.
62. Anton P Porsteinsson 1, George T Grossberg, Jacobo Mintzer, Jason T Olin. Memantine treatment in patients with mild to moderate
Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, doubleblind, placebo-controlled trial. Curr Alzheimer Res. 2008 Feb;5(1):83-9. doi: 10.2174/156720508783884576, PMID: 18288936.