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Acetylcholinesterase inhibitors (Galantamine, Rivastigmine, and Donepezil)

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NeuroPsychopharmacotherapy

Abstract

Galantamine, rivastigmine, and donepezil, inhibitors of acetylcholinesterase enzyme, are approved for the symptomatic management of Alzheimer’s disease. They inhibit the metabolism of acetylcholine, the cholinergic transmitter in brain regions responsible for cognition. Since cholinergic deficiency is found in individuals with Alzheimer’s disease, increasing the levels of acetylcholine can improve cholinergic neurotransmission. All three agents, which are absorbed by the oral route, inhibit acetylcholinesterase, whereas rivastigmine additionally inhibits butyrylcholinesterase. They do not alter the course of the disease, nor reverse its pathological changes. Adverse effects, particularly of the gastrointestinal tract and of behavioral changes, limit the dose in which they can be given. To avoid acute side effects, they are given in a small dose, which is gradually increased depending on the tolerability.

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References

  • Ali TB, Schieret TR, Reillu BM, Chen WY, Abagyan R. Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United States and Canada. PLoS One. 2015:e0144337. https://doi.org/10.1371/journal.pone.0144337.

  • Berk C, Sabbagh M. Broader considerations of higher doses of donepezil in the treatment of mild, moderate and severe Alzheimer’s disease. Int J Alzheimer’s disease. 2012;2012:707468. https://doi.org/10.1155/2012/707468.

    Article  CAS  Google Scholar 

  • Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev. 2019;6:CD001190.

    Google Scholar 

  • Birks JS, Chong LY, Evans JG, Cochrane Dementia and Cognitive Improvement Group. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2015;9:CD001191. https://doi.org/10.1002/14651858.CD001191.pub4.

    Article  PubMed  Google Scholar 

  • Carney G, Bassett K, Wright JM, Maclure M, McGuire N, Dormuth CR. Comparison of cholinesterase inhibitor safety in real-world practice. Alzheimer’s Dement Trans Res Clin Interv. 2019;5:732–9.

    Google Scholar 

  • Colovic MB, Krstic DZ, Pasti TDL, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11:315–35.

    Article  CAS  Google Scholar 

  • Contelles JM, Carreiras MDC, Rodriguez C, Villarroya M, Garcia AG. Synthesis and pharmacology of galantamine. Chem Rev. 2006;106:116–33.

    Article  Google Scholar 

  • Cui CC, Sun Y, Wang XY, Zhang Y, Xing Y. The effect of anti-dementia drugs on Alzheimer disease-induced cognitive impairment. A network meta-analysis. Medicine. 2019;98:27(e16091). https://doi.org/10.1097/MD0000000000016091.

    Article  Google Scholar 

  • Cummings J, Froelich L, Black SE, Bakchine S, Bellelli G, Molinuevo JL, et al. Randomized, double-blind, parallel-group, 48 week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs 10 cm2 in Alzheimer’s disease). Dement Geriatr Cogn Disord. 2012;33:341–53.

    Article  CAS  Google Scholar 

  • Desai AK, Grossberg GT. Rivastigmine for Alzheimer’s disease. Expert Rev Neurother. 2005;5:563–80.

    Article  CAS  Google Scholar 

  • Dou KX, Tan MS, Tan CC, Cao XP, Hou XH, Guo QH, Tan L, Mok V, Yu JT. Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: a network meta-analysis of 41 randomized controlled trials. Alzheimers Res Ther. 2018;10:126. https://doi.org/10.1186/s13195-018-0457-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ennakhil NB, Coste F, Xie L, Aigbogun MS, Wang Y, Kariburyo F, et al. A real-world analysis of treatment patterns for cholinesterase inhibitors and memantine among newly-diagnosed Alzheimer’s disease patients. Neurol Ther. 2017;6:131–44.

    Article  Google Scholar 

  • Froestl W, Muhs A, Pfeifer A. Cognitive enhancers (Nootropics). Part 2: drugs interacting with enzymes. J Alzheimers Dis. 2013;33:547–658.

    Article  CAS  Google Scholar 

  • Haake A, Nguyen K, Friedman L, Chakkamparambil B, Grossberg GT. An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease. Expert Opin Drug Saf. 2020;19:147–57.

    Article  CAS  Google Scholar 

  • Hong YJ, Han HJ, Youn YC, Park KW, Yang DW, Kim SY, et al. Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer’s disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial. Alzheimer’s Res Ther. 2019;11:37. https://doi.org/10.1186/s13195-019-0492-1.

    Article  Google Scholar 

  • Hwang TY, Ahn IS, Kim S, Kim DK. Efficacy of galantamine on cognition in mild-to-moderate Alzheimer’s dementia after failure to respond to donepezil. Psychiatry Investig. 2016;13:341–8.

    Article  CAS  Google Scholar 

  • Jann MW. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy. 2000;20:1–12.

    Article  CAS  Google Scholar 

  • Kaushik V, Smith ST, Mikobi E, Raji MA. Acetylcholinesterase inhibitors: beneficial effects on comorbidities in patients with Alzheimer’s disease. Am J Alzheimers Dis Other Dement. 2018;33:73–85. https://doi.org/10.1177/1533317517734352.

  • Khoirunisa V, Rusydi F, Kasai H, Gandaryus AG, Dipojono HK. A first principle study on the interaction between acetylcholinesterase and acetylcholine, and also rivastigmine in Alzheimer’s disease case. J Phys Conf Ser. 2016;739:012136. https://doi.org/10.1088/1742-6596/739/1/012136.

    Article  CAS  Google Scholar 

  • Khoury R, Rajamanickam J, Grossberg GT. An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine. Ther Adv Drug Saf. 2018;9:171–8.

    Article  CAS  Google Scholar 

  • Kim SH, Kandiah N, Hsu JL, Suthisisang C, Udommongkoi C, Dash A. Beyond symptomatic effects: potential of donepezil as a neuroprotective agent and disease modifier in Alzheimer’s disease. Br J Pharmacol. 2017;174:4224–32.

    Article  CAS  Google Scholar 

  • Kobayashi H, Ohnishi T, Nakagawa R, Yoshizawa K. The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: a Bayesian network meta-analysis. Int J Geriatr Psychiatry. 2016;31:892–904.

    Google Scholar 

  • Kroger E, Mouls M, Wilchesky M, Berkers M, Carmichael PH, Marum RV, Souverein P, Egberts T, Laroche ML. Adverse drug reactions reported with cholinesterase inhibitors: an analysis of 16 years of individual case safety reports from VigiBase. Ann Pharmacother. 2015; https://doi.org/10.1177/1060028015602274.

  • Li DD, Zhang YH, Zhang W, Zhao P. Meta-analysis of randomized controlled trials on the efficacy and safety of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. Front Neurosci. 2019;13:472. https://doi.org/10.3389/fnins.2019.00472.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maclagan LC, Bronskill SE, Guan J, Campitelli MA, Herrmann N, Lapane KL, Hogan DB, Amuah JE, Seits DP, Gill SS, Maxwell CJ. Predictors of cholinesterase discontinuation during the first year after nursing home admission. J Am Med Dir Assoc. 2018;19:P959–66.

    Article  Google Scholar 

  • Mucke HAM. The case of galantamine: repurposing and late blooming of a cholinergic drug. Future Sci. 2015;1:FS073. https://doi.org/10.4155/fso.15.73.

    Article  CAS  Google Scholar 

  • Nakamura Y, Imai Y, Shigeta M, Graf A, Shirahase T, Kim H, et al. A 24-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of the rivastigmine patch in Japanese patients with Alzheimer’s disease. Dement Geriatr Cogn Disord Extra. 2011;1:163–79.

    Article  Google Scholar 

  • Ohnishi T, Sakiyama Y, Okuri Y, Kimura Y, Sugiyama N, Saito T, Takashi M, Kobayashi T. Curr Alzheimer Res. 2014;11:110–8.

    Article  CAS  Google Scholar 

  • Ray B, Maloney B, Sambamurti K, Karnati HK, Nelson PT, Greig NH, Lahiri DK. Rivastigmine modifies the a-secretase pathway and potentially early Alzheimer’s disease. Transl Psychiatry. 2020;10:47. https://doi.org/10.1038/s41398-020-0709-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reeve E, Farrell B, Thompson W, Herrmann N, Sketris I, Magin PJ, et al. Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary. Med J Aust. 2019;210:174–9.

    Article  Google Scholar 

  • Santamaria TZ, Gomez PY, Galindo F, Gonzalez MG, Vazquez AO, Lopez ML. Pharmacogenetic studies in Alzheimer disease. Neurologia. 2020; https://doi.org/10.1016/j.nrl.2018.03.025.

  • Scott LJ, Goa KL. Galantamine. A review of its use in Alzheimer’s disease. Drugs. 2000;60:1095–122.

    Article  CAS  Google Scholar 

  • Shamsi A, Anwar S, Mohammad T, Alajmi MF, Hussain A, Rehman MT, Hasan GM, Islam A, Hassan MI. MARK4 inhibited by AChE inhibitors, donepezil and rivastigmine tartrate: insights into Alzheimer’s disease therapy. Biomol Ther. 2020;10:789. https://doi.org/10.3390/biom10050789.

    Article  CAS  Google Scholar 

  • Silvente LB, Castells X, Saez M, Barcelo MA, Olmo JG, Franch JV, Capella D. Discontinuation, efficacy and safety of cholinesterase inhibitors for Alzheimer’s disease: a meta-analysis and meta-regression of 43 randomized clinical trials enrolling 16 106 patients. Int J Neuropsychopharmacol. 2017;20:519–28.

    Article  Google Scholar 

  • Stoiljkovic M, Kelley C, Horvath TL, Hajos M. Neurophysiological signals as predictive translational biomarkers for Alzheimer’s disease treatment: effects of donepezil on neuronal network oscillations in TgF344-AD rats. Alzheimers Res Ther. 2018;10:105. https://doi.org/10.1186/s13195-018-0433-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugimoto H, Ogura H, Arai Y, Limura Y, Yamanishi Y. Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Jpn J Pharmacol. 2002;89:7–20.

    Article  CAS  Google Scholar 

  • Tan CC, Yu JT, Wang HF, Tan MS, Meng XF, Wang C, et al. Efficacy and safety of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;41:615–31.

    Article  CAS  Google Scholar 

  • Upadhyay SD, Ahmad Y, Kohli S. Review on pharmacological potential of galantamine. Pharmacogn Commun. 2020;10:63–6.

    Article  CAS  Google Scholar 

  • Wallin AK, Wattmo C, Minthon L. Galantamine treatment in Alzheimer’s disease: response and long-term outcome in a routine clinical setting. Neuropsych Dis Treat. 2011;7:565–76.

    Article  CAS  Google Scholar 

  • Williams BR, Nazarians A, Gill MA. A review of rivastigmine: a reversible cholinesterase inhibitor. Clin Ther. 2003;25:1634–53.

    Article  CAS  Google Scholar 

  • Winblad B, Cummings J, Andreasen N, Grossberg G, Onofrj M, Sadowsky C, et al. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease – rivastigmine patch versus capsule. Int J Geriatr Psychiatry. 2007;22:456–67.

    Article  Google Scholar 

  • Zeb MW, Riaz A, Szigeti K. Donepezil: a review of pharmacological characteristics and role in the management of Alzheimer’s disease. Clin Med Insights – Geriatr. 2017;10:1–14.

    Google Scholar 

  • Zhang X, Yu R, Wang H, Zheng R. Effects of rivastigmine hydrogen tartrate and donepezil hydrochloride on the cognitive function and mental behavior of patients with Alzheimer’s disease. Exp Ther Med. 2020;20:1789–95.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Endocrine and Diabetes Centre, Visakhapatnam, Andhra Pradesh, India

    Gumpeny R. Sridhar

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  1. Gumpeny R. Sridhar
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Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Würzburg, Bayern, Germany

    Christian Riederer

Section Editor information

  1. Szeged, Hungary

    Laszlo Vecsei

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Sridhar, G.R. (2021). Acetylcholinesterase inhibitors (Galantamine, Rivastigmine, and Donepezil). In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_418-1

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  • DOI: https://doi.org/10.1007/978-3-319-56015-1_418-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56015-1

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