Memantine and Cholinesterase Inhibitors: Complementary Mechanisms in the Treatment of Alzheimer’s Disease
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- 作者：Chris G. Parsons (1) (4)
Wojciech Danysz (2)
Andrzej Dekundy (2)
Irena Pulte (3) - 关键词：Acetylcholine ; Alzheimer’s disease ; Cholinesterase inhibitors ; Glutamate ; Mechanism of action ; Memantine
- 刊名：Neurotoxicity Research
- 出版年：2013
- 出版时间：October 2013
- 年：2013
- 卷：24
- 期：3
- 页码：358-369
- 全文大小：512KB
- 参考文献：1. Albin RL, Greenamyre JT (1992) Alternative excitotoxic hypotheses. Neurology 42:733-38
2. Albrecht M, Rammes G, Gravius A, Parsons CG (2008) Memantine reverses β-amyloid oligomers-induced deficits in long-term potentiation (LTP) in murine hippocampal slices. Poster presented at 38th Society for Neuroscience Annual Meeting, Nov 15-8, Washington, USA
3. Allen TG, Abogadie FC, Brown DA (2006) Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic-basal forebrain neurons. J Neurosci 26:1588-595
4. Atri A, Sherman S, Norman KA, Kirchhoff BA, Nicolas MM, Greicius MD, Cramer SC, Breiter HC, Hasselmo ME, Stern CE (2004) Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory task. Behav Neurosci 118:223-36
5. Atri A, Shaughnessy LW, Locascio JJ, Growdon JH (2008) Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 22:209-21
6. Atri A, Molinuevo JL, Lemming O, Wirth Y, Pulte I, Wilkinson D (2013) Memantine in patients with Alzheimer’s disease receiving donepezil: new analyses of efficacy and safety for combination therapy. Alzheimers Res Ther 5:6
7. Auld DS, Kornecook TJ, Bastianetto S, Quirion R (2002) Alzheimer’s disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 68:209-45
8. Barnes CA, Meltzer J, Houston F, Orr G, McGann K, Wenk GL (2000) Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Neuroscience 99:17-3
9. Bassil N, Thaipisuttikul P, Grossberg GT (2010) Memantine ER, a once-daily formulation for the treatment of Alzheimer’s disease. Expert Opin Pharmacother 11:1765-771
10. Bigl V, Woolf NJ, Butcher LL (1982) Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull 8:727-49
11. Birks J (2009) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 1:CD005593. doi:10.1002/14651858
12. Cacabelos R, Takeda M, Winblad B (1999) The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer’s disease. Int J Geriatr Psychiatry 14:3-7
13. Calabrese P, Essner U, F?rstl H (2007) Memantine (Ebixa?) in clinical practice—results of an observational study. Dement Geriatr Cogn Disord 24:111-17
14. Carnes KM, Fuller TA, Price JL (1990) Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular basal forebrain in the rat. J Comp Neurol 302:824-52
15. Chen H-SV, Pellegrini JW, Aggarwal SK, Lei SZ, Warach S, Jensen FE, Lipton SA (1992) Open-channel block of / N-methyl-d -aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 12:4427-436
16. Cummings JL, Schneider E, Tariot PN, Graham SM, Memantine MEM-MD-02 Study Group (2006) Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 67:57-3
17. Dantoine T, Auriacombe S, Sarazin M, Becker H, Pere JJ, Bourdeix I (2006) Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer’s disease who failed to benefit from previous cholinesterase inhibitor treatment. Int J Clin Pract 60:110-18
18. Danysz W, Parsons CG (2003) The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int J Geriatr Psychiatry 18:S23–S32
19. Danysz W, Parsons CG, Mobius HJ, Stoffler A, Quack G (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer’s disease—a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2:85-7
20. Davidsson P, Blennow K, Andreasen N, Eriksson B, Minthon L, Hesse C (2001) Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer’s disease. Neurosci Lett 300:157-60
21. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL (2007) Abeta oligomers induce neuronal oxidative stress through an / N-methyl-d -aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282:11590-1601
22. Di Angelantonio S, Bernardi G, Mercuri NB (2004) Donepezil modulates nicotinic receptors of substantia nigra dopaminergic neurones. Br J Pharmacol 141:644-52
23. Dijk SN, Francis PT, Stratmann GC, Bowen DM (1995) Cholinomimetics increase glutamate outflow via an action on the corticostriatal pathway: implications for Alzheimer’s disease. J Neurochem 65:2165-169
24. Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7-1
25. Drachman DA (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27:783-90
26. Drever BD, Riedel G, Platt B (2011) The cholinergic system and hippocampal plasticity. Behav Brain Res 221:505-14
27. Enz A, Gentsch C (2004) Co-administration of memantine has no effect on the in vitro or ex vivo determined acetylcholinesterase inhibition of rivastigmine in the rat brain. Neuropharmacology 47:408-13
28. Fadel J, Sarter M, Bruno JP (2001) Basal forebrain glutamatergic modulation of cortical acetylcholine release. Synapse 39:201-12
29. Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E, Donepezil MSAD Study Investigators Group (2001) A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology 57:613-20
30. Feldman HH, Schmitt FA, Olin JT, Memantine MEM-MD-02 Study Group (2006) Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment. Alzheimer Dis Assoc Disord 20:263-68
31. Fournier GN, Materi LM, Semba K, Rasmusson DD (2004) Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain. Neuroscience 123:785-92
32. Francis PT, Palmer AM, Sims NR, Bowen DM, Davison AN, Esiri MM, Neary D, Snowden JS, Wilcock GK (1985) Neurochemical studies of early-onset Alzheimer’s disease. Possible influence on treatment. N Engl J Med 313:7-1
33. Francis PT, Sims NR, Procter AW, Bowen DM (1993) Cortical pyramidal neurone loss may cause glutamatergic hypoactivity and cognitive impairment in Alzheimer’s disease: investigative and therapeutic perspectives. J Neurochem 60:1589-604
34. Frankiewicz T, Parsons CG (1999) Memantine restores long term potentiation impaired by tonic / N-methyl-d -aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices. Neuropharmacology 38:1253-259
35. Gauthier S, Wirth Y, M?bius HJ (2005) Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 20:459-64
36. Giacobini E (2003) Cholinergic function and Alzheimer’s disease. Int J Geriatr Psychiatry 18:S1–S5
37. Giacobini E, DeSarno P, Clark B, McIlhany M (1989) The cholinergic receptor system of the human brain: neurochemical and pharmacological aspects in aging and Alzheimer. Prog Brain Res 79:335-43
38. Gillette-Guyonnet S, Andrieu s, Nourhashemi F, Gardette V, Coley N, Cantet C, Gauthier S, Ousset PJ, Vellas B (2011) Long-term progression of Alzheimer’s disease in patients under antidementia drugs. Alzheimers Dement 7:579-92
39. Giovannini MG, Mutolo D, Bianchi L, Michelassi A, Pepeu G (1994) NMDA receptor antagonists decrease GABA outflow from the septum and increase acetylcholine outflow from the hippocampus—a microdialysis study. J Neurosci 14:1358-365
40. Greenamyre JT, Young AB (1989) Excitatory amino acids and Alzheimer’s disease. Neurobiol Aging 10:593-02
41. Grossberg GT, Manes F, Allegri R (2008) A multinational, randomized, double-blind, placebo-controlled parallel-group trial of memantine extended-release capsule (28?mg, once daily) in patients with moderate to severe Alzheimer’s disease. Alzheimers Dement 4:T793
42. Gupta RC, Dekundy A (2005) Memantine does not influence AChE inhibition in rat brain by donepezil or rivastigmine but does with DFP and metrifonate in in vivo studies. Drug Dev Res 64:71-1
43. Harris ME, Wang Y, Pedigo NW Jr, Hensley K, Butterfield DA, Carney JM (1996) Amyloid β peptide (25-5) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures. J Neurochem 67:277-86
44. Hartmann S, M?bius HJ (2003) Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. Int Clin Psychopharmacol 18:81-5
45. Hort J, O’Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, Sorbi S, Scheltens P (2010) EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol 17:1236-248
46. Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D, Holmes C, Hughes A (2012) Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 366:893-03
47. Joseph JA, Cutler R, Roth GS (1993) Changes in G protein-mediated signal transduction in aging and Alzheimer’s disease. Ann N Y Acad Sci 695:42-5
48. Keilhoff G, Wolf G (1992) Memantine prevents quinolinic acid-induced hippocampal damage. Eur J Pharmacol 219:451-54
49. Kenney JW, Gould TJ (2008) Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol 38:101-21
50. Klein WL, Lacor PN, De Felice FG, Ferreira ST (2007) Molecules that disrupt memory circuits in Alzheimer’s disease: the attack on synapses by Aβ oligomers (ADDLs). In: Bontempi B, Silva AJ, Christen Y (eds) Memories: molecules and circuits. Springer, Berlin, pp 155-79
51. Klyubin I, Wang Q, Reed MN, Irving EA, Upton N, Hofmeister J, Cleary JP, Anwyl R, Rowan MJ (2011) Protection against Abeta-mediated rapid disruption of synaptic plasticity and memory by memantine. Neurobiol Aging 32:614-23
52. Kornhuber J, Weller M (1997) Psychotogenicity and / N-methyl-d -aspartate receptor antagonism: implications for neuroprotective pharmacotherapy. Biol Psychiatry 41:135-44
53. Lachaine J, Beauchemin C, Legault M, Bineau S (2011) Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease. Can J Psychiatry 56:596-04
54. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL (2007) Aβ oligomers-induced aberrations in synapse composition, shape and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci 27:796-07
55. Lancelot E, Beal MF (1998) Glutamate toxicity in chronic neurodegenerative disease. Prog Brain Res 116:331-47
56. Lopez OL, Becker JT, Wahed AS, Saxton J, Sweet RA, Wolk DA, Klunk W, Dekosky ST (2009) Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry 80:600-07
57. Martinez-Coria H, Green K, Banerjee PK, LaFerla FM (2009) Combination of memantine and donepezil reverses cognitive deficits in transgenic mice with both amyloid-beta plaques and neurofibrillary tangles. Poster presented at 22nd Congress of the European College of Neuropsychopharmacology (ECNP), Sept 12-6, Istanbul, Turkey
58. Martinez-Coria H, Green KN, Billings LM, Kitazawa M, Albrecht M, Rammes G, Parsons CG, Gupta S, Banerjee P, LaFerla FM (2010) Memantine improves cognition and reduces Alzheimer’s-like neuropathology in transgenic mice. Am J Pathol 176:870-80
59. Mattson MP, Barger SW, Cheng B, Lieberburg I, Smith-Swintosky VL, Rydel RE (1993) β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease. Trends Neurosci 16:409-14
60. Mesulam MM, Mufson EJ (1984) Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey. Brain 107:253-74
61. Mewaldt SP, Ghoneim MM (1979) The effects and interactions of scopolamine, physostigmine and methamphetamine on human memory. Pharmacol Biochem Behav 10:205-10
62. Miguel-Hidalgo JJ, Alvarex XA, Cacabelos R, Quack G (2002) Neuroprotection by memantine against neurodegeneration induced by β-amyloid(1-0). Brain Res 958:210-21
63. Misztal M, Frankiewicz T, Parsons CG, Danysz W (1996) Learning deficits induced by chronic intraventricular infusion of quinolinic acid—protection by MK-801 and memantine. Eur J Pharmacol 296:1-
64. Moor E, Auth F, DeBoer P, Westerink BHC (1996) Septal and hippocampal glutamate receptors modulate the output of acetylcholine in hippocampus: a microdialysis study. J Neurochem 67:310-16
65. Nakagami Y, Oda T (2002) Glutamate exacerbates amyloid beta1-42-induced impairment of long-term potentiation in rat hippocampal slices. Jpn J Pharmacol 88:223-26
66. Neumeister KL, Riepe MW (2012) Synergistic effects of antidementia drugs on spatial learning and recall in the APP23 transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 30:245-51
67. Noda M, Nakanishi H, Akaike N (1999) Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. Neuroscience 92:1465-474
68. Nordberg A (2001) Nicotinic receptor abnormalities of Alzheimer’s disease: therapeutic implications. Biol Psychiatry 49:200-10
69. Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG (2011) The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine. Behav Brain Res 221:594-03
70. Palmer AM, Gershon S (1990) Is the neuronal basis of Alzheimer’s disease cholinergic or glutamatergic? FASEB J 4:2745-752
71. Parsons CG, Gruner R, Rozental J, Millar J, Lodge D (1993) Patch clamp studies on the kinetics and selectivity of / N-methyl-d -aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 32:1337-350
72. Parsons CG, Danysz W, Quack G (1998) Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect 11:523-69
73. Parsons CG, Danysz W, Bartmann A, Spielmanns P, Frankiewicz T, Hesselink M, Eilbacher B, Quack G (1999a) Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterization. Neuropharmacology 38:85-08
74. Parsons CG, Danysz W, Quack G (1999b) Memantine is a clinically well tolerated / N-methyl-d -aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38:735-67
75. Parsons CG, St?ffler A, Danysz W (2007) Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system—too little activation is bad, too much is even worse. Neuropharmacology 53:699-23
76. Patel L, Grossberg GT (2011) Combination therapy for Alzheimer’s disease. Drugs Aging 28:539-46
77. Periclou AP, Ventura D, Sherman T, Rao N, Abramowitz WT (2004) Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother 38:1389-394
78. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2:1457-459
79. Perry E, Walker M, Grace J, Perry R (1999) Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci 22:273-80
80. Petersen RC (1977) Scopolamine induced learning failures in man. Psychopharmacology 52:283-89
81. Popa RV, Pereira EF, Lopes C, Maelicke A, Albuquerque EX (2006) The / N-butylcarbamate derivative of galantamine acts as an allosteric potentiating ligand on alpha7 nicotinic receptors in hippocampal neurons: clinical implications for treatment of Alzheimer’s disease. J Mol Neurosci 30:227-32
82. Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT, Memantine MEM-MD-12 Study Group (2008) Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res 5:83-9
83. Reisberg B, Doody R, St?ffler A, Schmitt F, Ferris S, Mobius HJ, Memantine Study Group (2003) Memantine in moderate-to-severe Alzheimer’s disease. New Engl J Med 348:1333-341
84. Schmidtke K, Holthoff V, Kressig RW, Molinuevo JL (2011) Combination of Memantine and cholinesterase inhibitors in the treatment of AD. Neurology News 1:1-
85. Schmitt FA, van Dyck CH, Wichems CH, Olin JT, for the Memantine MEM-MD-02 Study Group (2006) Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: an exploratory reanalysis. Alzheimer Dis Assoc Disord 20:255-62
86. Shua-Haim J, Smith J, Picard F, Sedek G, Athalye S, Pommier F, Lefevre G (2008) Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer’s disease not affected by co-administration of memantine: an open-label, crossover, single-centre study. Clin Drug Investig 28:361-74
87. Sims NR, Bowen DM, Allen SJ, Smith CC, Neary D, Thomas DJ, Davison AN (1983) Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40:503-09
88. Szegedi V, Juhász G, Budai D, Penke B (2005) Divergent effects of Abeta1-42 on ionotropic glutamate receptor-mediated responses in CA1 neurons in vivo. Brain Res 1062:120-26
89. Takata K, Kitamura Y, Saeki M et al (2010) Galantamine-induced amyloid-{beta} clearance mediated via stimulation of microglial nicotinic acetylcholine receptors. J Biol Chem 285:40180-0191
90. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, Memantine Study Group (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. A randomized controlled trial. JAMA 291:317-24
91. Terry AV Jr, Buccafusco JJ (2003) The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 306:821-27
92. Thathiah A, De Strooper B (2009) G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in Alzheimer’s disease. Sci Signal 2:1-
93. Turrini P, Casu MA, Wong TP, De Koninck Y, Ribeiro-da-Silva A, Cuello AC (2001) Cholinergic nerve terminals establish classical synapses in the rat cerebral cortex: synaptic pattern and age-related atrophy. Neuroscience 105:277-85
94. van Dyck CH, Schmitt FA, Olin JT, Memantine MEM-MD-02 Study Group (2006) A responder analysis of memantine treatment in patients with Alzheimer disease maintained on donepezil. Am J Geriatr Psychiatry 14:428-37
95. Vidal JS, Lacombe JM, Dartigues JF, Pasquier F, Robert P, Tzourio C, Alperovitch A (2008) Memantine therapy for Alzheimer disease in real-world practice: an observational study in a large representative sample of French patients. Alzheimer Dis Assoc Disord 22:125-30
96. Wattmo C, Wallin AK, Londos E, Minthon L (2011) Predictors of long-term cognitive outcome in Alzheimer’s disease. Alzheimer’s Res Ther 3:23
97. Weinstock M (1999) Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs 12:307-23
98. Wenk GL, Danysz W, Mobley SL (1994) Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat. Brain Res 655:7-1
99. Wenk GL, Danysz W, Mobley SL (1995) MK-801, memantine and amantadine show neuroprotective activity in the nucleus basalis magnocellularis. Eur J Pharmacol 293:267-70
100. Wenk GL, Quack G, Moebius HJ, Danysz W (2000) No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci 66:1079-083
101. Wenk GL, Parsons CG, Danysz W (2006) Potential role of / N-methyl-d -aspartate receptors as executors of neurodegeneration resulting from diverse insults: focus on memantine. Behav Pharmacol 17:411-24
102. Weycker D, Taneja C, Edelsberg J, Erder MH, Schmitt FA, Setyawan J, Oster G (2007) Cost-effectiveness of memantine in moderate-to-severe Alzheimer’s disease patients receiving donepezil. Curr Med Res Opin 23:1187-197
103. Wilcock GK, Ballard CG, Cooper JA, Loft H (2008) Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry 69:341-48
104. Wilkinson D, Andersen HF (2007) Analysis of the effect of memantine in reducing the worsening of clinical symptoms in patients with moderate to severe Alzheimer’s disease. Dement Geriatr Cogn Disord 24:138-45
105. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J (2004) Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging 21:453-78
106. Willard LB, Hauss-Wegrzyniak B, Danysz W, Wenk GL (2000) The cytotoxicity of chronic neuroinflammation upon basal forebrain cholinergic neurons of rats can be attenuated by glutamatergic antagonism or cyclo-oxygenase-2 inhibition. Exp Brain Res 134:58-5
107. Winblad B, Jones RW, Wirth Y, St?ffler A, M?bius HJ (2007) Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials. Dement Geriatr Cogn Disord 24:20-7
108. Wu J, Anwyl R, Rowan MJ (1995) β-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. NeuroReport 6:2409-413
109. Wu M, Hajszan T, Xu C, Leranth C, Alreja M (2004) Group I metabotropic glutamate receptor activation produces a direct excitation of identified septohippocampal cholinergic neurons. J Neurophysiol 92:1216-225
110. Yao C, Raoufinia A, Gold M, Nye JS, Ramael S, Padmanabhan M, Walschap Y, Verhaeghe T, Zhao Q (2005) Steady-state pharmacokinetics of galantamine are not affected by addition of memantine in healthy subjects. J Clin Pharmacol 45:519-28
111. Zajaczkowski W, Frankiewicz T, Parsons CG, Danysz W (1997) Uncompetitive NMDA receptor antagonists attenuate NMDA-induced impairment of passive avoidance learning and LTP. Neuropharmacology 36:961-71 - 作者单位：Chris G. Parsons (1) (4)
Wojciech Danysz (2)
Andrzej Dekundy (2)
Irena Pulte (3)
1. In Vitro Pharmacology, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt, Germany
4. In Vitro Pharmacology, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt, Germany
2. In Vivo Pharmacology, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt, Germany
3. Global Clinical Research and Development CNS, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318, Frankfurt, Germany - ISSN：1476-3524
文摘
This review describes the preclinical mechanisms that may underlie the increased therapeutic benefit of combination therapy—with the N-methyl-d-aspartate receptor antagonist, memantine, and an acetylcholinesterase inhibitor (AChEI)—for the treatment of Alzheimer’s disease (AD). Memantine, and the AChEIs target two different aspects of AD pathology. Both drug types have shown significant efficacy as monotherapies for the treatment of AD. Furthermore, clinical observations indicate that their complementary mechanisms offer superior benefit as combination therapy. Based on the available literature, the authors have considered the preclinical mechanisms that could underlie such a combined approach. Memantine addresses dysfunction in glutamatergic transmission, while the AChEIs serve to increase pathologically lowered levels of the neurotransmitter acetylcholine. In addition, preclinical studies have shown that memantine has neuroprotective effects, acting to prevent glutamatergic over-stimulation and the resulting neurotoxicity. Interrelations between the glutamatergic and cholinergic pathways in regions of the brain that control learning and memory mean that combination treatment has the potential for a complex influence on disease pathology. Moreover, studies in animal models have shown that the combined use of memantine and the AChEIs can produce greater improvements in measures of memory than either treatment alone. As an effective approach in the clinical setting, combination therapy with memantine and an AChEI has been a welcome advance for the treatment of patients with AD. Preclinical data have shown how these drugs act via two different, but interconnected, pathological pathways, and that their complementary activity may produce greater effects than either drug individually.