Letter to the editor
Pharmacological aspects of galantamine for the treatment of Alzheimer's disease
Jae Kwang Kim1, Sang Un Park21Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Korea
2Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
EXCLI J 2017;16:Doc35
Galantamine is a natural product belonging to the isoquinoline alkaloid family of compounds. It was first discovered and isolated in the 1950s from Galanthus nivalis (common snowdrop) and Galanthus woronowii (Caucasian snowdrop), members of the Amaryllidaceae family (Marco and do Carmo Carreiras, 2006).
Alzheimer's disease (AD) is named after Dr. Alois Alzheimer, who first identified the disease in 1906. AD slowly destroys memory and thinking skills and is the most frequently diagnosed age-related neurodegenerative disorder (Prvulovic et al., 2010). Galantamine is an acetylcholinesterase (AChE) inhibitor and one of the most promising drugs available for the treatment of AD and various other memory impairments (Scott and Goa, 2000; Ago et al., 2011). Synthetic galantamine was first approved for the treatment of AD in Sweden in 2000 and was subsequently approved in the European Union and the United States (Heinrich and Lee Teoh, 2004). In the present report, we reviewed the most recent studies on the pharmacological activity of galantamine (Table 1(Tab. 1)) (References in Table 1: Hager et al., 2016; Hishikawa et al., 2016; Hwang et al., 2016; Wahba et al., 2016; Hanafy et al., 2016; Inden et al., 2016; Bezerra et al., 2016; Misra et al., 2016;Oka et al., 2016; Tokuchi et al., 2016; Wu et al., 2015; Nakano et al., 2015; Atanasova et al., 2015; Fornaguera et al., 2015; Woo et al., 2015; Bhattacharya et al., 2015; Jiang et al., 2015; Prins et al., 2014; Alexandrova et al., 2014; Furukawa et al., 2014; Caramelli et al., 2014; Koola et al., 2014; Kita et al., 2014; Hager et al., 2014; Bhattacharya et al., 2014; Richarz et al., 2014; Ramakrishnan et al., 2014).
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3A9A5919548).
Conflict of interest
The authors declare no conflict of interest.
1. Ago Y, Koda K, Takuma K, Matsuda T. Pharmacological aspects of the acetylcholinesterase inhibitor galantamine. J Pharmacol Sci. 2011;116:6-17.
2. Alexandrova EA, Alkondon M, Aracava Y, Pereira EF, Albuquerque EX. Galantamine prevents long-lasting suppression of excitatory synaptic transmission in CA1 pyramidal neurons of soman-challenged guinea pigs. Neurotoxicology. 2014;44:270-8.
3. Atanasova M, Stavrakov G, Philipova I, Zheleva D, Yordanov N, Doytchinova I. Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity. Bioorg Med Chem. 2015;23:5382-9.
4. Bezerra da Silva C, Pott A, Elifio-Esposito S, Dalarmi L, Fialho do Nascimento K, Moura Burci L, et al. Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on acetylcholinesterase inhibition in Dugesia tigrina. Molecules. 2016;21:53.
5. Bhattacharya S, Haertel C, Maelicke A, Montag D. Galantamine slows down plaque formation and behavioral decline in the 5XFAD mouse model of Alzheimer's disease. PLoS One. 2014;9(2):e89454.
6. Bhattacharya S, Maelicke A, Montag D. Nasal application of the Galantamine Pro-drug Memogain slows down plaque deposition and ameliorates behavior in 5X familial Alzheimer's Disease mice. J Alzheimers Dis. 2015;46:123-36.
7. Caramelli P, Laks J, Palmini AL, Nitrini R, Chaves ML, Forlenza OV, et al. Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study). Arq Neuropsiquiatr. 2014;72:411-7.
8. Fornaguera C, Feiner-Gracia N, Calderó G, García-Celma MJ, Solans C. Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases. Nanoscale. 2015;7:12076-84.
9. Furukawa S, Yang L, Sameshima H. Galantamine, an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia in newborn rats. Int J Dev Neurosci. 2014;37:52-7.
10. Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, et al. Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer's disease: post-hoc analysis of a randomized placebo-controlled study. Alzheimers Res Ther. 2016;8:47.
11. Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, et al. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease. Neuropsychiatr Dis Treat. 2014;10:391-401.
12. Hanafy AS, Farid RM, Helmy MW, El Gamal SS. Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer's disease management. Drug Deliv. 2016;23:3111-22.
13. Heinrich M, Lee Teoh H. Galanthamine from snowdrop-the development of a modern drug against Alzheimer's disease from local Caucasian knowledge. J Ethnopharmacol. 2004;92:147-62.
14. Hishikawa N, Fukui Y, Sato K, Ohta Y, Yamashita T, Abe K. Comprehensive effects of galantamine and cilostazol combination therapy on patients with Alzheimer's disease with asymptomatic lacunar infarction. Geriatr Gerontol Int. 2016 Aug 31. epub ahead of print. doi:10.1111/ggi.12870.
15. 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 Invest. 2016;13:341-8.
16. Inden M, Takata K, Yanagisawa D, Ashihara E, Tooyama I, Shimohama S, et al. α4 nicotinic acetylcholine receptor modulated by galantamine on nigrostriatal terminals regulates dopamine receptor-mediated rotational behavior. Neurochem Int. 2016;94:74-81.
17. Jiang D, Yang X, Li M, Wang Y, Wang Y. Efficacy and safety of galantamine treatment for patients with Alzheimer's disease: a meta-analysis of randomized controlled trials. J Neural Transm. 2015;122:1157-66.
18. Kita Y, Ago Y, Higashino K, Asada K, Takano E, Takuma K, et al. Galantamine promotes adult hippocampal neurogenesis via M₁ muscarinic and α7 nicotinic receptors in mice. Int J Neuropsychopharmacol. 2014;17:1957-68.
19. Koola MM, Buchanan RW, Pillai A, Aitchison KJ, Weinberger DR, Aaronson ST, et al. Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia. Schizophr Res. 2014;157:84-9.
20. Marco L, do Carmo Carreiras M. Galanthamine, a natural product for the treatment of Alzheimer's disease. Recent Pat CNS Drug Discov. 2006;1:105-11.
21. Misra S, Chopra K, Sinha VR, Medhi B. Galantamine-loaded solid-lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations. Drug Deliv. 2016;23:1434-43.
22. Nakano Y, Matsuzono K, Yamashita T, Ohta Y, Hishikawa N, Sato K, et al. Long-term efficacy of Galantamine in Alzheimer's Disease: the Okayama Galantamine Study (OGS). J Alzheimers Dis. 2015;47:609-17.
23. Oka M, Nakaaki S, Negi A, Miyata J, Nakagawa A, Hirono N, et al. Predicting the neural effect of switching from donepezil to galantamine based on single-photon emission computed tomography findings in patients with Alzheimer's disease. Psychogeriatrics. 2016;16:121-34.
24. Prins ND, van der Flier WA, Knol DL, Fox NC, Brashear HR, Nye JS, et al. The effect of galantamine on brain atrophy rate in subjects with mild cognitive impairment is modified by apolipoprotein E genotype: post-hoc analysis of data from a randomized controlled trial. Alzheimers Res Ther. 2014;6:47.
25. Prvulovic D, Hampel H, Pantel J. Galantamine for Alzheimer's disease. Expert Opin Drug Metab Toxicol. 2010;6:345-54.
26. Ramakrishnan L, Amatya C, DeSaer CJ, Dalhoff Z, Eggerichs MR. Galantamine reverses scopolamine-induced behavioral alterations in Dugesia tigrina. Invert Neurosci. 2014;14:91-101.
27. Richarz U, Gaudig M, Rettig K, Schauble B. Galantamine treatment in outpatients with mild Alzheimer's disease. Acta Neurol Scand. 2014;129:382-92.
28. Scott LJ, Goa KL. Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000;60:1095-122.
29. Tokuchi R, Hishikawa N, Matsuzono K, Takao Y, Wakutani Y, Sato K, et al. Cognitive and affective benefits of combination therapy with galantamine plus cognitive rehabilitation for Alzheimer's disease. Geriatr Gerontol Int. 2016;16:440-5.
30. Wahba SM, Darwish AS, Kamal SM. Ceria-containing uncoated and coated hydroxyapatite-based galantamine nanocomposites for formidable treatment of Alzheimer's disease in ovariectomized albino-rat model. Mater Sci Eng C Mater Biol Appl. 2016;65:151-63.
31. Woo FY, Basri M, Masoumi HR, Ahmad MB, Ismail M. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer's disease. Int J Nanomed. 2015;10:3879-86.
32. Wu Z, Zhao L, Chen X, Cheng X, Zhang Y. Galantamine attenuates amyloid-β deposition and astrocyte activation in APP/PS1 transgenic mice. Exp Gerontol. 2015;72:244-50.
Table 1: Recent studies on the pharmacological activity of galantamine