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Memantine in Treatment of AD

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Alzheimer’s Disease

Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

None of the currently available treatment strategies effectively alleviates symptoms and stabilizes disease in moderate to severe Alzheimer’s disease (AD). However, memantine* is a moderate-affinity, voltage-dependent, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has both demonstrated clinical benefit in improving individual symptoms of AD and produced preclinical evidence for neuroprotection in various models (1).

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References

  1. Committee for Proprietary Medicinal Products (CPMP): European Public Assessment Reports (EPAR) for Axura (CPMP/982/02 and CPMP/1604/02). London, 2002.

    Google Scholar 

  2. Cacabelos, R.; Takeda, M.; Winblad, B.: The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer’s disease. Int J Geriatr Psychiatry 1999; 14: 3–47.

    Article  PubMed  CAS  Google Scholar 

  3. Danysz, W. et al.: Neuroprotection and symptomatological action of memantine relevant for Alzheimer’s disease -a unified hypothesis on the mechanism of action. Neurotox Res 2000; 2: 85–98.

    Article  PubMed  CAS  Google Scholar 

  4. Winblad, B.; Poritis, N.: Memantine in severe dementia. Int J Geriatr Psychiatry 1999; 14: 135–146.

    Article  PubMed  CAS  Google Scholar 

  5. Orgogozo, J.M. et al.: Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002; 33: 1834–1839.

    Article  PubMed  CAS  Google Scholar 

  6. Wilcock, G.; Möbius, H.J.; Stöffler, A.: A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 2002; 17: 297–305.

    Article  PubMed  CAS  Google Scholar 

  7. Reisberg, B. et al.: Memantine, an uncompetitive NMDA antagonist, in patients with moderate to severe Alzheimer’s disease. N Engl J Med 2003; 348: 1333–1341.

    Article  PubMed  CAS  Google Scholar 

  8. Reisberg, B. et al.: Long-term treatment with the NMDA antagonist memantine: results of a 24-week, open-label extension study in moderately severe to severe Alzheimer’s disease. Neurobiol Aging 2002; 23: 5555, abstr 2039.

    Google Scholar 

  9. Internal communication, Forest Labs, New York, NY, 2002.

    Google Scholar 

  10. Chen, H.S.; Lipton, S.A.: Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol 1997; 499: 27–46.

    PubMed  CAS  Google Scholar 

  11. Rohrbacher, J.; Bijak, M.; Misgeld, U.: Suppression by memantine and amantadine of synaptic excitation intrastriatally evoked in rat neostriatal slices. Neurosci Lett 1994; 182: 95–98.

    Article  PubMed  CAS  Google Scholar 

  12. Parsons, C.G. et al.: Comparative patch-clamp studies with freshly dissociated rat hippocampal and striatal neurons on the NMDA receptor antagonistic effects of amantadine and memantine. Eur J Neurosci 1996; 8: 446–454.

    Article  PubMed  CAS  Google Scholar 

  13. Frankiewicz, T. et al.: Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices. Br J Pharmacol 1996; 117: 689–697.

    Article  PubMed  CAS  Google Scholar 

  14. Sobolevsky, A.I.; Koshelev, S.G.; Khodorov, B.I:. Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons. J Physiol 1998; 512: 47–60.

    Article  PubMed  CAS  Google Scholar 

  15. Frankiewicz, T.; Parsons, C.G.: Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg’ in hippocampal slices. Neuropharmacology 1999; 38: 1253–1259.

    Article  PubMed  CAS  Google Scholar 

  16. Blanpied, T.A. et al.: Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 1997; 77: 309–323.

    PubMed  CAS  Google Scholar 

  17. Bormann, J.: Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur J Pharmacol 1989; 166: 591–592.

    Article  PubMed  CAS  Google Scholar 

  18. Parsons, C.G. et al.: Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 1993; 32: 1337–1350.

    Article  PubMed  CAS  Google Scholar 

  19. Krieglstein, J.; Lippert, K.; Poch, G.: Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage. Neuropharmacology 1996; 35: 1737–1742.

    Article  PubMed  CAS  Google Scholar 

  20. Erdo, S.L.; Schafer, M.: Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate. Eur J Pharmacol 1991; 198: 215–217.

    Article  PubMed  CAS  Google Scholar 

  21. Weller, M.; Finiels-Marlier, F.; Paul, S.M.: NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. Brain Res 1993; 613: 143–148.

    Article  PubMed  CAS  Google Scholar 

  22. Pellegrini, 7.W.; Lipton, S.A.: Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity. Ann Neurol 1993; 33: 403–407.

    Article  PubMed  CAS  Google Scholar 

  23. Rao, V.L. et al.: Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 2001; 911: 96–100.

    Article  PubMed  CAS  Google Scholar 

  24. Gorgulu, A. et al.: Reduction of edema and infarction by memantine and MK-801 after focal cerebral ischaemia and reperfusion in rat. Acta Neurochir (Wien) 2000; 142: 1287–1292.

    Article  CAS  Google Scholar 

  25. Dogan, A. et al.: Protective effects of memantine against ischemia reperfusion injury in spontaneously hypertensive rats. Acta Neurochir (Wien) 1999; 141: 1107–1113.

    Article  CAS  Google Scholar 

  26. Seif el Nasr, M. et al.: Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur J Pharmacol 1990; 185: 19–24.

    Article  Google Scholar 

  27. Heim, C.; Sontag, K.H.: Memantine prevents progressive functional neurodegeneration in rats. J Neural Transm Suppl 1995; 46: 117–130.

    PubMed  CAS  Google Scholar 

  28. Stieg, P.E. et al.: Neuroprotection by the NMDA receptor-associated open channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. Eur J Pharmacol 1999; 375: 115–120.

    Article  PubMed  CAS  Google Scholar 

  29. Misztal, M. et al.: Learning deficits induced by chronic intraventricular infusion of quinolinic acid protection by MK801 and memantine. Eur J Pharmacol 1996; 296: 1–8.

    Article  PubMed  CAS  Google Scholar 

  30. Wenk, G.L.; Danysz, W.; Mobley, S.L.: MK-801, memantine and amantadine show neuroprotective activity in the nucleus basalis magnocellularis. Eur J Pharmacol 1995; 293: 267–270.

    Article  PubMed  CAS  Google Scholar 

  31. Schwenkreis, P. et al.: Influence of the N-methyl-D-aspartate antagonist memantine on human motor cortex excitability. Neurosci Lett 1999; 270: 137–140.

    Article  PubMed  CAS  Google Scholar 

  32. Schugens, M.M. et al.: The NMDA antagonist memantine impairs classical eyeblink conditioning in humans. Neurosci Lett 1997; 224: 57–60.

    Article  PubMed  CAS  Google Scholar 

  33. Schulz, H. et al.: The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study. Neuropsychobiology 1996; 33: 32–40.

    Article  PubMed  CAS  Google Scholar 

  34. Rammsayer, T.H.: Effects of pharmacologically induced changes in NMDA-receptor activity on long-term memory in humans. Learn Mem 2001, 28; 8: 20–25.

    Article  Google Scholar 

  35. Van der Kam, P.; Mol, F.; Wimmers, M.F.H.C.: Beoordelingsschaal voor oudere Patienten (BOP). Van Loghum Slaterus, Deuenter, The Netherlands, 1971.

    Google Scholar 

  36. Wimo, A. et al.: Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer’s Disease. Pharmacoeconomics, 2003; 21: 327–340.

    Article  PubMed  CAS  Google Scholar 

  37. Möbius, H.J. and Stöffler, A.: Memantine in vascular dementia. Int Psychogeriatrics 2003; 15 (suppl. 1): 207–213.

    Article  Google Scholar 

  38. Wilcock, G. et al.: Neuro-radiolgical findings and the magnitude of cognitive benefit by memantine treatment. A subgroup analysis of two placebo-controlled clinical trials in vascular dementia. Eur J Neuropsychopharm 2001; 10 (suppl 3): S360.

    Google Scholar 

  39. Möbius, H.J.: Pharmacologic rationale for memantine in chronic cerebral hypoperfusion, especially vascular dementia. Alzheimer’s Dis Assoc Disord 1999; 13 (suppl 3): 172–178.

    Article  Google Scholar 

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Authors
  1. Hans Jörg Möbius
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Editors and Affiliations

  1. The University of Oklahoma College of Medicine, USA

    Ralph W. Richter MD, FACP (Clinical Professor of Neurology and Psychiatry, Director) (Clinical Professor of Neurology and Psychiatry, Director)

  2. Alzheimer’s Disease Research Unit, St. John Medical Center, Tulsa, OK, USA

    Ralph W. Richter MD, FACP (Clinical Professor of Neurology and Psychiatry, Director) (Clinical Professor of Neurology and Psychiatry, Director)

  3. Tulsa, OK, USA

    Brigitte Zoeller Richter DiplPharm (Pharmacist, Publicist) (Pharmacist, Publicist)

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© 2004 Springer Science+Business Media New York

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Möbius, H.J. (2004). Memantine in Treatment of AD. In: Richter, R.W., Richter, B.Z. (eds) Alzheimer’s Disease. Current Clinical Neurology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-661-4_23

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  • DOI: https://doi.org/10.1007/978-1-59259-661-4_23

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-4485-9

  • Online ISBN: 978-1-59259-661-4

  • eBook Packages: Springer Book Archive

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