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Amantadine and the glutamate hypothesis of schizophrenia Experiences in the treatment of neuroleptic malignant syndrome

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Summary

Amantadine was introduced for the pharmacological management of neuroleptic malignant syndrome (NMS) because of its beneficial effects in Parkinson's disease which were attributed to dopaminomimetic properties. While the dopaminomimetic effects of amantadine are weak under experimental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of the glutamate receptor. Amantadine has psychotomimetic properties in patients with Parkinson's disease and normal controls. Two of four patients who received amantadine for NMS suffered an exacerbation of their psychiatric illness. Our observations support the glutamate hypothesis of schizophrenia which suggests that reduced glutamatergic transmission causes a relative dopaminergic excess in the basal ganglia and the limbic system.

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Author notes

  1. J. Kornhuber

    Present address: Department of Psychiatry, University of Würzburg, Federal Republic of Germany

  2. M. Weller

    Present address: Clinical Neuroscience Branch, National Institute of Mental Health, Building 10, Room 3N256, 20892, Bethesda, MD, USA

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  1. Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    M. Weller

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  1. J. Kornhuber
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Kornhuber, J., Weller, M. Amantadine and the glutamate hypothesis of schizophrenia Experiences in the treatment of neuroleptic malignant syndrome. J. Neural Transmission 92, 57–65 (1993). https://doi.org/10.1007/BF01245162

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  • DOI: https://doi.org/10.1007/BF01245162

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