Skip to main content

AAN.com

Articles

May 1, 1998

Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease

L. Verhagen Metman, MD, P. Del Dotto, MD, P. van den Munckhof, BS, J. Fang, MD, M. M. Mouradian, MD, and T. N. Chase, MDAuthors Info & Affiliations

May 1998 issue

50 (5) 1323-1326

https://doi.org/10.1212/WNL.50.5.1323

Abstract

Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD).

Background: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties.

Methods: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews.

Results: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries.

Conclusions: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.

Verhagen Metman L, Locatelli ER, Bravi D, Mouradian MM, Chase TN. Apomorphine responses in Parkinson's disease and the pathogenesis of motor complications. Neurology 1997;48:369-372.

2.

Chase TN, Engber TM, Mouradian MM. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson's disease. Adv Neurol 1996;69:497-501.

3.

Engber TM, Papa SM, Boldry RC, Chase TN. NMDA receptor blockade reverses motor response alterations induced by levodopa. Neuroreport 1994;5:2586-2588.

4.

Papa SM, Chase TN. Levodopa induced dyskinesias improved by a glutamate antagonist in parkinsonian monkeys. Ann Neurol 1996;39:574-578.

5.

Verhagen Metman L, Blanchet PJ, Mouradian MM, Chase TN. Dextromethorphan and levodopa combination therapy in parkinsonian patients with response fluctuations. Mov Disord 1996;11:184. Abstract.

6.

Blanchet PJ, Verhagen Metman L, Mouradian MM, Chase TN. Acute pharmacologic blockade of dyskinesias in Parkinson's disease. Mov Disord 1996;11:580-581.

7.

Kornhuber J, Bormann J, Hubers M, Rusche K, Riederer P. Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur J Pharmacol 1991;206:297-300.

8.

Kornhuber J, Quack G, Danysz W, et al. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology 1995;34:713-721.

9.

Kurlan R, Rothfield AB, Woodward WR, et al. Erratic gastric emptying of levodopa may cause "random" fluctuations of parkinsonian mobility. Neurology 1988;38:418-421.

10.

Danysz W, Gossel M, Zajaczkowski W, Dill D, Quack G. Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats? Case of amantadine and memantine. J Neural Transm Park Dis Dement Sect 1994;7:155-166.

11.

Fleiss JL. The measurement of interrater agreement. In: Fleiss JL, ed. Statistical methods for rates and proportions. New York: Wiley and Sons, 1981:212-236.

12.

Rajput AH, Uitti RJ, Lang AE, Rajput AH. Amantadine ameliorates levodopa induced dyskinesia. Neurology 1997;48:328. Abstract.

13.

Adler C, Stern MB, Hurtig HI. Amantadine in advanced Parkinson's disease: good use of an old drug. J Neurol 1997;244:336-337.

14.

Freudenreich O, McEvoy JP. Added amantadine may diminish tardive dyskinesia in patients requiring continued neuroleptics. J Clin Psychiatry 1995;56:173. Letter.

15.

Silver H, Geraisy N, Schwartz M. No difference in the effect of biperiden and amantadine on parkinsonian- and tardive dyskinesia-type involuntary movements: a double-blind cross-over, placebo-controlled study in medicated chronic schizophrenic patients. J Clin Psychiatry 1995;56:167-170.

16.

Shannon KM, Goetz CG, Carroll VS, Tanner CM, Klawans HL. Amantadine and motor fluctuations in chronic Parkinson's disease. Clin Neuropharmacol 1987;10:522-526.

17.

Von Voigtlander PF, Moore KE. Dopamine: release from the brain in vivo by amantadine. Science 1971;174:408-410.

18.

Bailey EV, Stone TW. The mechanism of action of amantadine in parkinsonism: a review. Arch Int Pharmacodyn Ther 1975;216:246-262.

19.

Quack G, Hesselink M, Danysz W, Spanagel R. Microdialysis studies with amantadine and memantine on pharmacokinetics and effects on dopamine turnover. J Neural Transm Suppl 1995;46:97-105.

20.

Nastuk WL, Su P, Doubilet P. Anticholinergic and membrane activities of amantadine in neuromuscular transmission. Nature 1976;264:76-79.

21.

Hauser RA, Olanow CW. Orobuccal dyskinesia associated with trihexyphenidyl therapy in a patient with Parkinson's disease. Mov Disord 1993;8:512-514.

22.

Kornhuber J, Weller M, Schoppmeyer K, Riederer P. Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 1994;43:91-104.

23.

Kornhuber J, Schoppmeyer K, Riederer P. Affinity of 1-aminoadamantanes for the sigma binding site in postmortem human frontal cortex. Neurosci Lett 1993;163:129-131.

24.

Debonnel G, de Montigny C. Modulation of NMDA and dopaminergic neurotransmissions by sigma ligands: possible implications for the treatment of psychiatric disorders. Life Sci 1996;58:721-734.

Information & Authors

Information

Published In

Neurology^®

Volume 50 • Number 5 • May 1998

Pages: 1323-1326

PubMed: 9595981

Copyright

© 1998.

Publication History

Published online: May 1, 1998

Published in print: May 1998

Permissions

Request permissions for this article.

Request Permissions

Authors

Affiliations & Disclosures

L. Verhagen Metman, MD

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

P. Del Dotto, MD

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

P. van den Munckhof, BS

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

J. Fang, MD

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

M. M. Mouradian, MD

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

T. N. Chase, MD

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

View all articles by this author

Notes

Address correspondence and reprint requests to Dr. Thomas N. Chase, National Institutes of Health, Building 10, Room 5C104, 10 CENTER DR MSC 1406, Bethesda, MD 20892-1406.

Metrics & Citations

Metrics

Citation information is sourced from Crossref Cited-by service.

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By

- Sara Kulik,
- Sylwia Golba,
- Izabela Matuła,
- Ewa Stodolak-Zych,
- Roksana Kurpanik,
Amantadine-Heparin-Polypyrrole as a Promising Drug Delivery Reservoir with a Biological Approach, Coatings, 14, 11, (1389), (2024).https://doi.org/10.3390/coatings14111389
Crossref
- Halak Shukla,
- Diana John,
- Shuvomoy Banerjee,
- Anand Krishna Tiwari,
Drug repurposing for neurodegenerative diseases, Clinical Application of Repurposed Drugs, (249-319), (2024).https://doi.org/10.1016/bs.pmbts.2024.03.035
Crossref
- Margherita Fabbri,
- Vanessa Rousseau,
- Jean-Christophe Corvol,
- Agnès Sommet,
- Florence Tubach,
- Yann De Rycke,
- Nathalie Bertille,
- Yajiththa Selvarasa,
- Stephanie Carvalho,
- Véronique Chaigneau,
- Christine Brefel-Courbon,
- Fabienne Ory-Magne,
- Samuel Tessier,
- Melissa Tir,
- Matthieu Bereau,
- Wassilios G. Meissner,
- Claire Thiriez,
- Ana Marques,
- Philippe Remy,
- Vincent Schneider,
- Elena Moro,
- Luc Defebvre,
- Jean Luc Houeto,
- Stephane Prange,
- Alexandre Eusebio,
- Christian Geny,
- Solène Frismand,
- Philippe Damier,
- Caroline Giordana Reuther,
- Giovanni Castelnovo,
- Isabelle Benatru,
- Anne Doe De Maindreville,
- Sophie Drapier,
- David Maltête,
- Ouhaid Lagha-Boukbiza,
- Olivier Rascol,
- Mickael Aubignat,
- Eloi Magnin,
- Pr Pierre Burbaud,
- Pr Dominique Guehl,
- Alexandra Foubert-Samier,
- Brice Laurens,
- Thomas Boraud,
- Sylvain Vergnet,
- David Bendetowicz,
- Thomas Palpacuer,
- Bérengère Debilly,
- Philippe Derost,
- Charlotte Beal,
- Hayet Salhi,
- Alice Dormeuil,
- Aimée Petit,
- Alban Gravier,
- Gwendoline Dupont,
- Lucie Garnier,
- Valérie Fraix,
- Anna Castrioto,
- Sara Meoni,
- Nicolas Carriere,
- Teodor Danaila,
- Chloé Laurencin,
- Stéphane Thobois,
- Jean-Philippe Azulay,
- Frédérique Fluchere,
- Mahmoud Charif,
- Marie-Christine Picot,
- Lucie Hopes,
- Anne-Gaelle Corbille,
- Tiphaine Rouaud,
- Pascal Derkinderen,
- Cosmin Alecu,
- Charlotte Heraud,
- Marie De Verdal,
- Bertrand Degos,
- Graziella Mangone,
- Sara Sambin,
- Aymeric Lanore,
- Thomas Courtin,
- Louise-Laure Mariani,
- David Bendetowicz,
- Fouad Khoury,
- Poornima Menon,
- Florence Cormier-Dequaire,
- Emmanuel Flamand-Roze,
- David Grabli,
- Elodie Hainque,
- Marie Vidhaillet,
- Aurélie Meneret,
- Cécile Delorme,
- Cendrine Foucard,
- Florian Von Raison,
- Alexis Elbaz,
- Andreas Hartmann,
- Vincent Leclercq,
- Solène Ansquer,
- Frederique Leh,
- Marion Leclercq,
- Guillaume Costentin,
- undefined Lagha Boukbiza,
- Christine Brefel Courbon,
- Clemence Leung,
- Hélène Catala,
- Astrid Causel,
- Emilie Gaiffe,
- Sandrine Dupouy,
- Sandrine Villars,
- Wei-Ho Lai,
- Rachida Bari,
- Damien Chevanne,
- Elodie Durand,
- Isabelle Rieu,
- Stephane Bernard,
- Corinne Garsault,
- Noel Boudjema,
- Pascale Grebent,
- Andrea Kistner,
- Pierre Pelissier,
- Valérie Santraine,
- Thomas Gaudin,
- Pierre Boutet,
- Catherine Caire,
- Manel Nouira,
- Claudia Verna,
- Amory Jardel,
- Salomé Puisieux,
- Guillemette Clement,
- Lili Le Monnier,
- Régis Frenais,
- Séverine Le Dily,
- Rachel Chaigneau,
- Vanessa Ferrier,
- Elodie David,
- Leslie Fra,
- Elsa Foucaran,
- Carole Dongmo-Kenfack,
- Florence Beauzor,
- Mickael Le,
- Sonia Messar,
- Sophie Liot,
- Emilie Rabois,
- Margaux Bonnaire-Verdier,
- Françoise Kestens,
- Rozenn Gourhan,
- Sandra Lopez-Alfaro,
- Jean-François Houvenaghel,
- Mélanie Alexandre,
- Christine Bourdonnais,
- Linda Vernon,
- Ahmed Boumediene,
- Céline Julie,
- Aurette Lobstein,
- Nadine Longato,
- Marie-Pierre Mitterle,
- Clélie Philips,
- Hugo Rummel,
- Stéphanie Bras,
- Estelle Harroch,
- Claudia Gillet,
Amantadine use in the French prospective NS-Park cohort, Journal of Neural Transmission, 131, 7, (799-811), (2024).https://doi.org/10.1007/s00702-024-02772-4
Crossref
- Olha Shuklinova,
- Sibylle Neuhoff,
- Sebastian Polak,
How PBPK Can Help to Understand Old Drugs and Inform their Dosing in Elderly: Amantadine Case Study , Clinical Pharmacology & Therapeutics, 116, 1, (225-234), (2024).https://doi.org/10.1002/cpt.3276
Crossref
- Jamir Pitton Rissardo,
- Nilofar Murtaza Vora,
- Irra Tariq,
- Amna Mujtaba,
- Ana Letícia Fornari Caprara,
Deep Brain Stimulation for the Management of Refractory Neurological Disorders: A Comprehensive Review, Medicina, 59, 11, (1991), (2023).https://doi.org/10.3390/medicina59111991
Crossref
- Natalia E. Owen,
- Roger A. Barker,
- Zanna J. Voysey,
Sleep Dysfunction in Huntington’s Disease: Impacts of Current Medications and Prospects for Treatment, Journal of Huntington's Disease, 12, 2, (149-161), (2023).https://doi.org/10.3233/JHD-230567
Crossref
- Idan Avigdori,
- Kuldeep Singh,
- Natalia Fridman,
- Mark Gandelman,
Nitrenium ions as new versatile reagents for electrophilic amination, Chemical Science, 14, 43, (12034-12040), (2023).https://doi.org/10.1039/D3SC04268E
Crossref
- Amos D. Korczyn,
Drug treatment of Parkinson's disease, Dialogues in Clinical Neuroscience, 6, 3, (315-322), (2022).https://doi.org/10.31887/DCNS.2004.6.3/akorczyn
Crossref
- Imane Frouni,
- Philippe Huot,
Glutamate Modulation for the Treatment of Levodopa Induced Dyskinesia: A Brief Review of the Drugs Tested in the Clinic, Neurodegenerative Disease Management, 12, 4, (203-214), (2022).https://doi.org/10.2217/nmt-2021-0055
Crossref
- Roberta Arb Saba,
- Débora Palma Maia,
- Francisco Eduardo Costa Cardoso,
- Vanderci Borges,
- Luiz Augusto F. Andrade,
- Henrique Ballalai Ferraz,
- Egberto Reis Barbosa,
- Carlos Roberto de Mello Rieder,
- Delson José da Silva,
- Hsin Fen Chien,
- Tamine Capato,
- Ana Lúcia Rosso,
- Carlos Frederico Souza Lima,
- José Marcelo Ferreia Bezerra,
- Denise Nicaretta,
- Orlando Graziani Povoas Barsottini,
- Clécio Godeiro-Júnior,
- Lorena Broseghini Barcelos,
- Rubens Gisbert Cury,
- Mariana Spitz,
- Sônia Maria César Azevedo Silva,
- Marcus Vinicius Della Colletta,
Guidelines for Parkinson’s disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms, Arquivos de Neuro-Psiquiatria, 80, 3, (316-329), (2022).https://doi.org/10.1590/0004-282x-anp-2021-0219
Crossref
See more

View Options

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login

Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
[email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

advertisement

Impact Factor

We are pleased to announce that Neurology^® was awarded a new Impact Factor of 8.4. Explore our latest research and articles and join our community of distinguished authors by submitting your work .

Open Review Pilot Project

Explore peer reviews, author responses, and editor comments on selected articles.

Learn More

Letters to the Editor

The Letters section represents an opportunity for ongoing author debate and post-publication peer review. View our submission guidelines for Letters to the Editor before submitting your comment.

Submit a Letter for this article

View full text|Download PDF