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AMPA Potentiation as a Treatment Option for Alzheimer’s Disease

  • Amy S. Chappell
  • Michael M. Witte
Chapter
Part of the Current Clinical Neurology book series (CCNEU)

Abstract

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor modulators, although still in their infancy from a therapeutic standpoint, have the potential to correct the deficits associated with cognitive disorders such as Alzheimer’s disease (AD). This chapter reviews the AMPA receptor’s role in long-term potentiation and thus in learning and memory, and describes the AMPA potentiators currently under development.

Keywords

Attention Deficit Hyperactivity Disorder Glutamate Receptor Attention Deficit Hyperactivity Disorder Synaptic Strength Nootropic Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bliss, T.P.; Collingridge, G.L.: A synaptic model memory; long-term potentiation in the hippocampus. Nature 1993; 361: 31–39.PubMedCrossRefGoogle Scholar
  2. 2.
    Greenmyre, J.T.: The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 1986; 43: 1058–1062.CrossRefGoogle Scholar
  3. 3.
    Dingledine, R. et al.: The glutamate receptor ion channels. Pharmacol Rev 1999; 51: 7–61.PubMedGoogle Scholar
  4. 4.
    Burrone, J.; Murthy, V.N.: Synaptic plasticity: rush hour traffic in the AMPA lanes. Curr Biol 2001; 11: R274 - R277.PubMedCrossRefGoogle Scholar
  5. 5.
    Nowak, L. et al.: Magnesium gates glutamate-activated channels in mouse central neurons. Nature 1984; 307: 462–465.PubMedCrossRefGoogle Scholar
  6. 6.
    Hollmann, M.; Heinemann, S.: Cloned glutamate receptors. Ann Rev Neurosci 1994; 17: 31–108.PubMedCrossRefGoogle Scholar
  7. 7.
    Bleakman, D.; Lodge, D.: Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 1998; 37: 1187–1204.PubMedCrossRefGoogle Scholar
  8. 8.
    Beattie, E.C. et al.: Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci 2000; 3: 12.Google Scholar
  9. 9.
    Löscher, C.; Frerking, M.: Restless AMPA receptors: implications for synaptic transmission and plasticity. Trends Neurosci 2001; 24: 11.CrossRefGoogle Scholar
  10. 10.
    Ito, I. et al.: Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam. J Physiol 1990; 424: 533–543.PubMedGoogle Scholar
  11. 11.
    Copani, A. et al.: Nootropic drugs positively modulate oa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures. J Neurochem 1992; 58: 1199–1204.PubMedCrossRefGoogle Scholar
  12. 12.
    Zivkovic. I. et al.: 7-Chloro-3-methyl-3–4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition by attenuating DL- amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor desensitization. J Pharmacol Exp Ther 1995; 272: 300–309.PubMedGoogle Scholar
  13. 13.
    Yamada, K. et al.: Prolongation of latencies for passive avoidance responses in rats treated with aniracetam or piracetam. Pharmacol Biochem Behav 1985; 22: 645–684.PubMedCrossRefGoogle Scholar
  14. 14.
    Senin, U. et al.: Aniracetam (Ro 13–5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical trial. Eur Neuropsychopharmacol 1991; 1: 511–517.PubMedCrossRefGoogle Scholar
  15. 15.
    Maina, G. et al.: Oxiracetam in the treatment of primary degenerative and multi-infarct dementia: a double-blind, placebo-controlled study. Neuropsychobiology 1989; 21: 141–145.PubMedCrossRefGoogle Scholar
  16. 16.
    Petkov, V.D. et al.: Age-related differences in memory and in the memory effects of nootropic drugs. Acta Physiol Pharmacol Bulgarica 1990; 16: 28–36.Google Scholar
  17. 17.
    Staubli, U.; Rogers, G.; Lynch, G: Facilitation of glutamate receptors enhances memory. Proc NatlAcad Sci USA 1994; 91: 777–781.CrossRefGoogle Scholar
  18. 18.
    Thompson, D.M. et al.: 7-Chloro-3-methyl-3–4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA-21), a cogener of aniracetam, potently abates pharmacologically-induced cognitive impairments in patas monkeys. Proc NatlAcad Sci USA 1995; 92: 7667–7671.CrossRefGoogle Scholar
  19. 19.
    Gouliaev, A.H.; Senning, A.: Piracetam and other structurally related nootropics. Brain Res Rev. 1994; 19: 180–222.PubMedCrossRefGoogle Scholar
  20. 20.
    Szabadits, P.; Mike, A.; Vizi, E.S.: Modulation of agonist-evoked responses of hippocampal AMPA receptors by IDRA 21 and cyclothiazide (abstr 143.8). World Congr Pharmacol 2002.Google Scholar
  21. 21.
    Yamada, K.A.: AMPA receptor activation potentiated by the AMPA modulator 1-BCP is toxic to cultured rat hippocampal neurons. Neurosci Lett 1998; 249: 119–122.PubMedCrossRefGoogle Scholar
  22. 22.
    Granger, R. et al.: A drug that facilitates glutamatergic transmission reduces exploratory activity and improves performance in a learning-dependent task. Synapse 1993; 15: 326–329.PubMedCrossRefGoogle Scholar
  23. 23.
    Bahr, B.A. et al.: Survival signaling and selective neuroprotection through glutamatergic neurotransmission. Exp Neurol 2002; 174: 37–47.PubMedCrossRefGoogle Scholar
  24. 24.
    Lauterborn, J.C. et al.: Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 2000; 20: 8–21.PubMedGoogle Scholar
  25. 25.
    Ingvar, M. et al.: Enhancement by an ampakine of memory encoding in humans. Exp Neurol 1997; 146: 553–559.PubMedCrossRefGoogle Scholar
  26. 26.
    Lynch, G. et al.: Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans. Exp Neurobiol 1997; 145: 89–92.CrossRefGoogle Scholar
  27. 27.
    Urbanics, R.: Neurodegenerative Drug Discovery and Development New Directions. IDDB Meeting Report, July 18–19, 2001, London, UK.Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Amy S. Chappell
  • Michael M. Witte

There are no affiliations available

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