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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1996 Sep;61(3):259–264. doi: 10.1136/jnnp.61.3.259

Amantadine hydrochloride treatment in heredodegenerative ataxias: a double blind study.

M I Botez 1, T Botez-Marquard 1, R Elie 1, O L Pedraza 1, K Goyette 1, R Lalonde 1
PMCID: PMC486548  PMID: 8795596

Abstract

OBJECTIVE: A group of 27 patients with Friedreich's ataxia and another group of 30 patients with olivopontocerebellar atrophies were each randomly divided into two subgroups, one receiving placebo and the other amantadine hydrochloride (AH; 200 mg daily) for three to four months. METHODS: The effect of double blind treatment was evaluated by simple visual and auditory reaction time (RT) and movement time (MT) for both right and left hands. RESULTS: The subgroup with olivopontocerebellar atrophies receiving AH showed significant improvement on seven out of eight variables studied by analysis of covariance. In patients with Friedreich's ataxia, improvement was definitely less. Treatment remained contraindicated for those with cardiomyopathies or drug intolerance. CONCLUSION: The rationale of AH use in heredodegenerative ataxias can be explained by its replacement effect (dopamine release) and by direct involvement of N-methyl-D-aspartate (NMDA) in glutamate mediated neurotoxicity in cerebellar granular cells; memantine, an AH analogue, is a potent blocker of NMDA receptors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amalric M., Koob G. F. Depletion of dopamine in the caudate nucleus but not in nucleus accumbens impairs reaction-time performance in rats. J Neurosci. 1987 Jul;7(7):2129–2134. doi: 10.1523/JNEUROSCI.07-07-02129.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ambrozi L., Danielczyk W. Treatment of impaired cerebral function in psychogeriatric patients with memantine--results of a phase II double-blind study. Pharmacopsychiatry. 1988 May;21(3):144–146. doi: 10.1055/s-2007-1014666. [DOI] [PubMed] [Google Scholar]
  3. BENTON A. L., BLACKBURN H. L. Practice effects in reaction-time tasks in brain-injured patients. J Abnorm Psychol. 1957 Jan;54(1):109–113. doi: 10.1037/h0047176. [DOI] [PubMed] [Google Scholar]
  4. Boje K. M., Wong G., Skolnick P. Desensitization of the NMDA receptor complex by glycinergic ligands in cerebellar granule cell cultures. Brain Res. 1993 Feb 19;603(2):207–214. doi: 10.1016/0006-8993(93)91239-o. [DOI] [PubMed] [Google Scholar]
  5. Bormann J. Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur J Pharmacol. 1989 Aug 3;166(3):591–592. doi: 10.1016/0014-2999(89)90385-3. [DOI] [PubMed] [Google Scholar]
  6. Botez M. I., Attig E., Vézina J. L. Cerebellar atrophy in epileptic patients. Can J Neurol Sci. 1988 Aug;15(3):299–303. doi: 10.1017/s0317167100027785. [DOI] [PubMed] [Google Scholar]
  7. Botez M. I., Botez T., Elie R., Attig E. Role of the cerebellum in complex human behavior. Ital J Neurol Sci. 1989 Jun;10(3):291–300. doi: 10.1007/BF02333774. [DOI] [PubMed] [Google Scholar]
  8. Botez M. I., Gravel J., Attig E., Vézina J. L. Reversible chronic cerebellar ataxia after phenytoin intoxication: possible role of cerebellum in cognitive thought. Neurology. 1985 Aug;35(8):1152–1157. doi: 10.1212/wnl.35.8.1152. [DOI] [PubMed] [Google Scholar]
  9. Botez M. I., Léveillé J., Lambert R., Botez T. Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis. Eur Neurol. 1991;31(6):405–412. doi: 10.1159/000116705. [DOI] [PubMed] [Google Scholar]
  10. Botez M. I., Young S. N., Botez T., Pedraza O. L. Treatment of heredo-degenerative ataxias with amantadine hydrochloride. Can J Neurol Sci. 1991 Aug;18(3):307–311. doi: 10.1017/s0317167100031863. [DOI] [PubMed] [Google Scholar]
  11. Botez M. I., Young S. N., Rotez T., Courchesne Y. Treatment of Friedreich's ataxia with amantadine. Neurology. 1989 May;39(5):749–750. doi: 10.1212/wnl.39.5.749-b. [DOI] [PubMed] [Google Scholar]
  12. Deutch A. Y., Elsworth J. D., Roth R. H., Goldstein M., Deutsch A. Y. 3-Acetylpyridine results in degeneration of the extrapyramidal and cerebellar motor systems: loss of the dorsolateral striatal dopamine innervation. Brain Res. 1990 Sep 10;527(1):96–102. doi: 10.1016/0006-8993(90)91065-o. [DOI] [PubMed] [Google Scholar]
  13. Efthimiopoulos S., Giompres P., Valcana T. Kinetics of dopamine and noradrenaline transport in synaptosomes from cerebellum, striatum and frontal cortex of normal and reeler mice. J Neurosci Res. 1991 Aug;29(4):510–519. doi: 10.1002/jnr.490290411. [DOI] [PubMed] [Google Scholar]
  14. Erdö S. L., Schäfer 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 Jun 6;198(2-3):215–217. doi: 10.1016/0014-2999(91)90625-z. [DOI] [PubMed] [Google Scholar]
  15. Filla A., De Michele G., Orefice G., Santorelli F., Trombetta L., Banfi S., Squitieri F., Napolitano G., Puma D., Campanella G. A double-blind cross-over trial of amantadine hydrochloride in Friedreich's ataxia. Can J Neurol Sci. 1993 Feb;20(1):52–55. doi: 10.1017/s0317167100047417. [DOI] [PubMed] [Google Scholar]
  16. Goetz C. G., Tanner C. M., Klawans H. L. The pharmacology of olivopontocerebellar atrophy. Adv Neurol. 1984;41:143–148. [PubMed] [Google Scholar]
  17. Gualtieri T., Chandler M., Coons T. B., Brown L. T. Amantadine: a new clinical profile for traumatic brain injury. Clin Neuropharmacol. 1989 Aug;12(4):258–270. [PubMed] [Google Scholar]
  18. Hamsher K., Benton A. L. The reliability of reaction time determinations. Cortex. 1977 Sep;13(3):306–310. doi: 10.1016/s0010-9452(77)80040-3. [DOI] [PubMed] [Google Scholar]
  19. Henneberry R. C., Novelli A., Cox J. A., Lysko P. G. Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease. Ann N Y Acad Sci. 1989;568:225–233. doi: 10.1111/j.1749-6632.1989.tb12512.x. [DOI] [PubMed] [Google Scholar]
  20. Horiguchi J., Inami Y., Shoda T. Effects of long-term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. Clin Neuropharmacol. 1990 Feb;13(1):84–88. doi: 10.1097/00002826-199002000-00009. [DOI] [PubMed] [Google Scholar]
  21. Jensen A. R. Spearman's g: links between psychometrics and biology. Ann N Y Acad Sci. 1993 Nov 17;702:103–129. doi: 10.1111/j.1749-6632.1993.tb17244.x. [DOI] [PubMed] [Google Scholar]
  22. Kish S. J., Robitaille Y., el-Awar M., Clark B., Schut L., Ball M. J., Young L. T., Currier R., Shannak K. Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy. Neurology. 1992 Aug;42(8):1573–1577. doi: 10.1212/wnl.42.8.1573. [DOI] [PubMed] [Google Scholar]
  23. Kornhuber J., Bormann J., Retz W., Hübers M., Riederer P. Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol. 1989 Aug 3;166(3):589–590. doi: 10.1016/0014-2999(89)90384-1. [DOI] [PubMed] [Google Scholar]
  24. Ladurner G., Tschinkel M., Klebl H., Lytwin H. Reaction time in cerebrovascular disease. Arch Gerontol Geriatr. 1985 Dec;4(4):373–379. doi: 10.1016/0167-4943(85)90044-5. [DOI] [PubMed] [Google Scholar]
  25. Lopes-Cendes I., Andermann E., Attig E., Cendes F., Bosch S., Wagner M., Gerstenbrand F., Andermann F., Rouleau G. A. Confirmation of the SCA-2 locus as an alternative locus for dominantly inherited spinocerebellar ataxias and refinement of the candidate region. Am J Hum Genet. 1994 May;54(5):774–781. [PMC free article] [PubMed] [Google Scholar]
  26. Louilot A., Le Moal M. Lateralized interdependence between limbicotemporal and ventrostriatal dopaminergic transmission. Neuroscience. 1994 Apr;59(3):495–500. doi: 10.1016/0306-4522(94)90171-6. [DOI] [PubMed] [Google Scholar]
  27. Monto A. S., Gunn R. A., Bandyk M. G., King C. L. Prevention of Russian influenza by amantadine. JAMA. 1979 Mar 9;241(10):1003–1007. [PubMed] [Google Scholar]
  28. Oertel W. H. Neurotransmitters in the cerebellum. Scientific aspects and clinical relevance. Adv Neurol. 1993;61:33–75. [PubMed] [Google Scholar]
  29. Oke A., Lewis R., Adams R. N. Hemispheric asymmetry of norepinephrine distribution in rat thalamus. Brain Res. 1980 Apr 21;188(1):269–272. doi: 10.1016/0006-8993(80)90575-2. [DOI] [PubMed] [Google Scholar]
  30. Panagopoulos N. T., Papadopoulos G. C., Matsokis N. A. Dopaminergic innervation and binding in the rat cerebellum. Neurosci Lett. 1991 Sep 16;130(2):208–212. doi: 10.1016/0304-3940(91)90398-d. [DOI] [PubMed] [Google Scholar]
  31. Peterson P. L., Saad J., Nigro M. A. The treatment of Friedreich's ataxia with amantadine hydrochloride. Neurology. 1988 Sep;38(9):1478–1480. doi: 10.1212/wnl.38.9.1478. [DOI] [PubMed] [Google Scholar]
  32. Polinsky R. J., Brown R. T., Burns R. S., Harvey-White J., Kopin I. J. Low lumbar CSF levels of homovanillic acid and 5-hydroxyindoleacetic acid in multiple system atrophy with autonomic failure. J Neurol Neurosurg Psychiatry. 1988 Jul;51(7):914–919. doi: 10.1136/jnnp.51.7.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sawaguchi T. Catecholamine sensitivities of neurons related to a visual reaction time task in the monkey prefrontal cortex. J Neurophysiol. 1987 Nov;58(5):1100–1122. doi: 10.1152/jn.1987.58.5.1100. [DOI] [PubMed] [Google Scholar]
  34. Spirduso W. W., MacRae H. H., MacRae P. G., Prewitt J., Osborne L. Exercise effects on aged motor function. Ann N Y Acad Sci. 1988;515:363–375. doi: 10.1111/j.1749-6632.1988.tb33010.x. [DOI] [PubMed] [Google Scholar]
  35. Taghzouti K., Le Moal M., Simon H. Suppression of noradrenergic innervation compensates for behavioral deficits induced by lesion of dopaminergic terminals in the lateral septum. Brain Res. 1991 Jun 21;552(1):124–128. doi: 10.1016/0006-8993(91)90669-m. [DOI] [PubMed] [Google Scholar]
  36. Tucker D. M., Williamson P. A. Asymmetric neural control systems in human self-regulation. Psychol Rev. 1984 Apr;91(2):185–215. [PubMed] [Google Scholar]
  37. Von Voigtlander P. F., Moore K. E. Dopamine: release from the brain in vivo by amantadine. Science. 1971 Oct 22;174(4007):408–410. doi: 10.1126/science.174.4007.408. [DOI] [PubMed] [Google Scholar]
  38. Wadia N. H., Swami R. K. A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families). Brain. 1971;94(2):359–374. doi: 10.1093/brain/94.2.359. [DOI] [PubMed] [Google Scholar]

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