Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease

Summary

Memantine is a 1-amino-adamantane derivative which has been proposed to be useful in the treatment of Parkinson's disease. Its beneficial effect has been related to its novel properties as an NMDA receptor blocker which can neutralize the effect of glutamate at striatal and subthalamic levels. In the present study, conducted in an open-fashion, 14 parkinsonian patients with motor fluctuations taking L-dopa, were given a supplement of memantine 30 mg/day. After one month, 10 patients completed the treatment (4 discontinued it due to abdominal pain, psychomotor agitation, confusion and dizziness). In 5 patients, the main parkinsonian features improved significantly (1 point or more on the Webster scale). In 6 patients, “off” episodes improved (from daily mean of 273 minutes, to 172 minutes). In summary, memantine addition to parkinsonian features, could form a basis for novel therapeutic strategies directed to neutralize the effects of glutamate at striatal and subthalamic levels.

This is a preview of subscription content, log in to check access.

References

  1. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12: 366–375

  2. Barbeau A (1981) The use of L-dopa in Parkinson's disease. A 20 year follow-up. Trends Pharmacol Sci 2: 297–299

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

  4. Carlsson M, Carlsson A (1989) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm 75: 221–226

  5. Eshel Y, Korczyn AD (1979) Amantadine antagonism of oxotremorine effects. J Neural Transm 46: 79–83

  6. Fahn S, Isgreen WP (1975) Long-term evaluation of amantadine and levodopa combination in parkinsonism by double-blind cross-over analysis. Neurology 25: 695–700

  7. Grimes JD (1984) Bromocriptine in Parkinson's disease. Results obtained with high and low-dose therapy. Can J Neurol Sci 11: 225–228

  8. Klockgether T, Turski L (1989) Excitatory amino acids and the basal ganglia: implications for the therapy of Parkinson's disease. Trends Neurosci 12: 285–286

  9. Klockgether T, Turski L (1990) NMDA antagonist potentiate antiparkinsonian actions of L-dopa in monoamine depleted rats. Ann Neurol 28: 539–546

  10. Kornhuber J, Bormann J, Retz W, Hübers M, Riederer P (1989) Memantine displaces [3H] MK-801 at therapeutic concentrations in post mortem human frontal cortex. Eur J Pharmacol 166: 589–590

  11. Kornhuber J, Bormann J, Hübers M, Rusche K, Riederer P (1991) Effects of the 1-amine-adamantanes at the MK-801 binding site of the NMDA receptor gated ion channel: a human postmortem brain study. Eur J Pharmacol (Mol Pharmacol Sect) 206: 297–300

  12. Mehta AK, Ticku MK (1990) Role of N-methyl-D-aspartate (NMDA) receptors in experimental catalepsy in rats. Life Sci 46: 37–42

  13. Olney JW, Price MT, Lubruyere J, Salles KS, Friedrich G, Mueller M, Silverman E (1987) Anti-parkinsonian agents are phencyclidine agonists and N-methyl-aspartate antagonists. Eur J Pharmacol 142: 319–320

  14. Rabey JM, Streifler M, Treves T, Korczyn AD (1989) A long-term comparative study of lisuride and levodopa in Parkinson's disease. In: Calne DB, Comi G, Crippa D, Horowski R, Trabucchi M (eds) Parkinsonism and aging. Raven Press, New York, pp 261–267

  15. Riederer P, Lange KW, Kornhuber J, Danielczyk W (1991) Pharmacotoxic psychosis after memantine in Parkinson's disease. Lancet 338: 1022–1023

  16. Schmidt WJ, Bubser M (1989) Anti-cataleptic effects of the N-methyl aspartate antagonist MK-801. Pharmacol Biochem Behav 32: 621–623

  17. Schmidt WJ, Bubser M, Hauber W (1990) Excitatory amino acids and Parkinson's disease. Trends Neurosci 13: 46–47

  18. Schneider E, Fischer PA, Clemens R, Balzereit F, Fünfgeld EW, Haase HJ (1984) Effects of ral memantine on symptoms of Parkinson's disease. Dtsch Med Wochenschr 109: 987–990

  19. Turski L, Bressler K, Retting KJ, Löschmann PA, Wachtel H (1991) Protection of substantia nigra from, MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 349: 414–418

  20. Webster DD (1968) Critical analysis of the disability in Parkinson's disease. Med Treat (NY) 5: 257–282

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rabey, J.M., Nissipeanu, P. & Korczyn, A.D. Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease. J Neural Transm Gen Sect 4, 277–282 (1992). https://doi.org/10.1007/BF02260076

Download citation

Keywords

  • Memantine
  • NMDA receptor antagonists
  • Parkinson's disease