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N-Methyl-D-Aspartate Antagonists, Schizophrenia, and Neuroleptic Malignant Syndrome-Reply

J. Timothy Greenamyre, MD, PHD
Arch Neurol. 1992;49(9):901-901. doi:10.1001/archneur.1992.00530330018008
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In Reply.  —I appreciate the comments by Weller and Kornhuber on our article.1 Although we confined our review to the potential use of N-methyl-d-aspartate (NMDA) antagonists in Parkinson's disease only, we certainly agree with the notion that these agents may be beneficial in other conditions. While it is well known that sudden withdrawal of dopaminergic antiparkinsonian medications may precipitate neuroleptic malignant syndrome (NMS),2 it is less widely appreciated that abrupt cessation of amantadine (a commonly used antiparkinsonian medication and a noncompetitive NMDA antagonist) may be associated with a profound exacerbation of parkinsonism3 and a condition marked by severe rigidity (J.T.G., unpublished observations, 1992), even with continued therapy with levodopa or a dopamine agonist. Could this represent a forme fruste or variant of NMS? Perhaps the full NMS is not seen in these cases because of the fact that there is ongoing dopaminergic therapy. It

REFERENCES

Greenamyre JT, O'Brien CF.  N-methyl-D-aspartate antagonists in the treatment of Parkinson's disease . Arch Neurol . 1991;;48:977-981.
Addonizio G, Susman VL, Roth SD.  Neuroleptic malignant syndrome: review and analysis of 115 cases . Biol Psychiatry . 1987;;22:1004-1020.
Weiner WJ, Lang AE. Movement Disorders: A Comprehensive Survey . Mount Kisco, NY: Futura Publishing Co; 1989;:92.
Klockgether T, Turski L.  NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats . Ann Neurol . 1990;: 28;539-546.
Klockgether T, Turski L, Zhang ZM, Gash DM, Kurlan R, Greenamyre JT.  The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys , Ann Neurol . 1991;;30:717-723.
Javitt DC, Zukin SR.  Recent advances in the phencyclidine model of schizophrenia . Am J Psychiatry . 1991;;148:1301-1308.
Kim JS, Kornhuber HH, Schmid-Burgk W,  Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia . Neurosci Lett . 1980;;20:379-382.
Kornhuber J, Mack-Burkhardt F, et al.  [3H]MK-801 binding sites in postmortem brain regions of schizophrenic patients . J Neural Transm . 1989;;77:231-236.
Nussenzveig IZ, Javitt DC, Silipo GS, Herescolevy H, Lindenmayer JP, Zukin SR. High-dose glycine in the treatment of schizophrenia. Presented at the Annual Meeting of the American Psychiatric Association; May 4, 1992; Washington, DC.

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Greenamyre JT, O'Brien CF.  N-methyl-D-aspartate antagonists in the treatment of Parkinson's disease . Arch Neurol . 1991;;48:977-981.
Addonizio G, Susman VL, Roth SD.  Neuroleptic malignant syndrome: review and analysis of 115 cases . Biol Psychiatry . 1987;;22:1004-1020.
Weiner WJ, Lang AE. Movement Disorders: A Comprehensive Survey . Mount Kisco, NY: Futura Publishing Co; 1989;:92.
Klockgether T, Turski L.  NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats . Ann Neurol . 1990;: 28;539-546.
Klockgether T, Turski L, Zhang ZM, Gash DM, Kurlan R, Greenamyre JT.  The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys , Ann Neurol . 1991;;30:717-723.
Javitt DC, Zukin SR.  Recent advances in the phencyclidine model of schizophrenia . Am J Psychiatry . 1991;;148:1301-1308.
Kim JS, Kornhuber HH, Schmid-Burgk W,  Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia . Neurosci Lett . 1980;;20:379-382.
Kornhuber J, Mack-Burkhardt F, et al.  [3H]MK-801 binding sites in postmortem brain regions of schizophrenic patients . J Neural Transm . 1989;;77:231-236.
Nussenzveig IZ, Javitt DC, Silipo GS, Herescolevy H, Lindenmayer JP, Zukin SR. High-dose glycine in the treatment of schizophrenia. Presented at the Annual Meeting of the American Psychiatric Association; May 4, 1992; Washington, DC.

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