Psychiatr. pro Praxi, 2004; 3: 162-168

Memantin - necholinergní alternativa léčby Alzheimerovy a vaskulární demence

prof. MUDr. Jaromír ©vestka DrSc
Psychiatrická klinika LF MU a FN Brno

Keywords: memantine, NMDA antagonists, Alzheimer#s dementia, vascular dementia.

Published: December 31, 2004  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
©vestka J. Memantin - necholinergní alternativa léčby Alzheimerovy a vaskulární demence. Psychiatr. praxi. 2004;9(3):162-168.

Excesivní uvolňování glutamatu při Alzheimerově a vaskulární demenci vede k excitotoxickému poąkození neuronů v CNS. Memantin účinkuje jako antagonista glutamatových NMDA receptorů a brání neurotoxicitě glutamatu, rovněľ ?-amyloidu a jeho tvorbě stejně jako ? proteinu. V klinických zkouąkách byl memantin účinným v léčbě Alzheimerovy a vaskulární demence a zpomaloval jejich progresi. Upravoval kognitivní funkce, vigilitu, denní aktivity nemocných a zvýąením jejich autonomie sniľoval spotřebu pomoci pečovatelů. Memantin byl velmi dobře snáąen a z neľádoucích účinků se nejčastěji vyskytly insomnie, závratě, cefalgie a u méně neľ 5% léčených halucinace. Memantin je prokázaně účinným kognitivem pro léčbu i těľąích forem Alzheimerovy demence a lehčí aľ středně těľké vaskulární demence s postiľením menąích cerebrálních cév.

Memantine - a noncholinergic alternative of treatment for Alzheimer-s and vascular dementia

Excessive release of glutamate in Alzheimer-s and vascular dementia leads to excitotoxic damage to CNS neurons. Memantine acts as a glutamate NMDA receptor antagonist and blocks glutamate and ?-amyloid neurotoxicity and synthesis of ?-amyloid and ? proteins. Clinical tests have shown memantine as effective in treatment of Alzheimer-s and vascular dementia and as slowing their progression. It adjusted cognitive functions, vigility, and daily activities of patients, and reduced the need for the help of caregivers by increasing patient autonomy. Memantine was tolerated very well and the most frequent side effects included insomnia, dizziness, headache, and hallucinations in less than 5% of patients. Memantine has been shown to be an effective cognitive enhancer to treat even severe forms of Alzheimer-s dementia and mild to medium severe vascular dementias with minor cerebral blood vessels defects.

Download citation

References

  1. Ambrozi L, Danielczyk W. Treatment of impaired cerebral function in psychogeriatric patients with memantine: Results of a phase III double-blind study. Pharmacopsychiatry 1988; 21: 144-146. Go to original source... Go to PubMed...
  2. Butterfield DA, Pocernich CB. The glutamatergic system and Alzheimer´s disease. Therapeutic implications. CNS Drugs 2003; 17: 641-652. Go to original source... Go to PubMed...
  3. Danysz W, Parsons CG, Möbius HJ, Stöffler A, Quack G. Neuroprotective and symptomatological action of memantine relevant for Alzheimer´s disease - a unified glutamatergic hypothesis on the mechanism of action. Neurotoxicity Res 2000; 2: 85-97. Go to original source... Go to PubMed...
  4. Ditzler K. Efficacy and tolerability of memantine in patients with dementia syndrome. A double-blind, placebo-controlled trial. Drug Res 1991; 41: 773-780.
  5. Görtelmeyer R, Erbler H. Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo-controlled study. Drug Res 1992; 42: 904-913.
  6. Greenamyre JT, Maragos EF, Albin RL, Renney JB, Young AB. Glutamate transmission and toxicity in Alzheimer´s disease. Prog Neuro-Psych Biol Psych 1988; 12: 421-430. Go to original source... Go to PubMed...
  7. Iqbal K, Li K, Sengupta A, Grundke-Iqbal I. Memantine restores okadaic acid-induced changes in protein phosphatase-2A, CAMK-II, and tau hyperphosphorylation in rat. J Neurochem 2003; 85 (Suppl. 1): 43. Go to original source...
  8. Jarvis B, Figgitt DP. Memantine. Drugs Aging 2003; 20: 465-476. Go to original source... Go to PubMed...
  9. Kornhuber J, Bormann J, Retz W, Hubers M, Riederer P. Memantine displaces [3H] MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 1989; 166: 589-590. Go to original source... Go to PubMed...
  10. Koh JY, Yang LL, Cotman CW. Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitoxic damage. Brain Res 1990; 533: 315-320. Go to original source... Go to PubMed...
  11. Lahiri DK, Alley GM, Morgan C, Banerjee P, Farlow M. Effect of memantine on levels of the amyloid beta peptide in cell cultures (Abstract). Eur Neuropsychopharmacol 2003; 13 (Suppl. 4): 391. Go to original source...
  12. Marvanova M, Lakso M, Pirhonen J, Nawa H, Wong G, Castrén E. The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Nerosci 2001; 18: 247-258. Go to original source... Go to PubMed...
  13. Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE. ?-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitoxicity. J Neurosci 1992; 12: 376-389. Go to original source... Go to PubMed...
  14. Miguel-Hidalgo JJ, Alvarez XA, Quack G, Cacabelos R. Protection by memantine againts Abeta (1-40) induced neurodegeneration in CA1 subfield. Neurobiol Aging 1998; 19: 542-545.
  15. Möbius HJ, Reisberg B, Schmitt F, Doody R. Long-term efficacy and safety from treatment with the NMDA antagonist memantine: Results of a 24-week, open-label extension study in moderate to severe Alzheimer´s disease (Abstract). Eur Neuropsychopharmacology 2003; 13 (Suppl. 4): 388. Go to original source...
  16. Orgogozo JM, Rigaud AS, Stöffler A, Möbius HJ, Forette F. 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. Go to original source... Go to PubMed...
  17. Pantev M, Ritter R, Görtelmeyer R. Clinical and behavioral evaluation in long-term care patients with mild to moderate dementia under memantine treatment. Zeitschr Gerontopsychol Psychiatr 1996; 6: 103-107.
  18. Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data. Neuropsychopharmacology 1999; 38: 735-767. Go to original source... Go to PubMed...
  19. Rammes M, Ferrari U, Ziegelgansberger W, Parsons CG. The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexenes antagonize 5-HT3 receptor currents in cultured HEK293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett 2001; 306: 81-84. Go to original source... Go to PubMed...
  20. Rao VLR, Dogan A, Todd KG, Bowen KK, Dempsey RJ. Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 2001; 911: 96-100. Go to original source... Go to PubMed...
  21. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, for the Memantine Study Group. Memantine in moderate-to-severe Alzheimer´s disease. The New England Journal of Medicine 2003; 348: 1333-1341. Go to original source... Go to PubMed...
  22. Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer´s disease. CNS Drugs Reviews 2003; 9: 275-308. Go to original source... Go to PubMed...
  23. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer´s disease already receiving donepezil. A randomized controlled trial. JAMA 2004; 291: 317-324. Go to original source... Go to PubMed...
  24. Wilcock G, Möbius HJ, Stöffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM 500). Int Clin Psychopharmacol 2002; 17: 297-305. Go to original source... Go to PubMed...
  25. Wimo A, Winblad B, Stöffler A, Wirth Y, Möbius HJ. Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer´s disease. Pharmacoeconomics 2003; 21: 327-340. Go to original source... Go to PubMed...
  26. Winblad B, Poritis N. Memantine in severe dementia: Results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 1999; 14: 135-146. Go to original source...
  27. Winblad B, Jelic V. Treating the full spectrum of dementia with memantine. Int J Geriatr Psychiatry 2003; 18 (Suppl. 1): 41-46. Go to original source... Go to PubMed...




Psychiatry for Practice

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.