N-Methyl-d-Aspartate Antagonists in the Treatment of Parkinson's Disease

doi:10.1001/archneur.1991.00530210109030

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Vol. 48 No. 9, September 1991

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N-Methyl-d-Aspartate Antagonists in the Treatment of Parkinson's Disease

J. Timothy Greenamyre, MD, PhD; Christopher F. O'Brien, MD

Arch Neurol. 1991;48(9):977-981.

Abstract

• Current long-term treatment of Parkinson's disease isinadequate, and improved symptomatic and neuroprotective therapiesare needed. Recent interest has focused on the use of antagonistsof the N-methyl-D-aspartate (NMDA) subtype of glutamate receptorin Parkinson's disease. Abnormally increased activity of thesubthalamic nucleus is postulated to play a central pathophysiologicalrole in the signs of Parkinson's disease, and NMDA antagonistsmay provide a means of decreasing this activity selectively.Like dopaminergic agonists, NMDA antagonists can reverse theakinesia and rigidity associated with monoamine depletion orneuroleptic-induced catalepsy. Very low doses of NMDA antagonistsmarkedly potentiate the therapeutic effects of dopaminergicagonists. There is evidence that the beneficial effects of anticholinergicdrugs and amantadine may be mediated, in part, by NMDA receptorblockade. Moreover, NMDA antagonists provide profound protectionof dopaminergic neurons of the substantia nigra in the MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and methamphetaminemodels of Parkinson's disease. The clinical use of NMDA antagonistsmay prove useful in Parkinson's disease to treat symptoms andretard disease progression.

Author Affiliations

From the Movement and Inherited Neurological Disorders Unit, Department of Neurology (Drs Drs Greenamyre and O'Brien), Department of Neurobiology and Anatomy (Dr Greenamyre), and Department of Pharmacology (Dr Greenamyre), University of Rochester (NY) Medical Center.

Footnotes

Accepted for publication March 28, 1991.

Reprint requests to Department of Neurology, University of RochesterMedical Center, 601 Elmwood Ave, Box 673, Rochester, NY 14642(Dr Greenamyre).

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