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Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPA-antagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.

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Author notes

  1. P. -A. Löschmann

    Present address: Department of Neuropsychopharmacology, Schering AG, P.O.B. 65 03 11, D-W-1000, Federal Republic of Germany

Authors and Affiliations

  1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College, London, UK

    K. W. Lange & P. Jenner

  2. Research Laboratories, Schering AG, Berlin, Federal Republic of Germany

    P. -A. Löschmann, M. Kunow, K. -J. Rettig, L. Turski & H. Wachtel

  3. University Department of Clinical Neurology, Institute of Neurology, The National Hospital, London, UK

    C. D. Marsden

  4. A F B Comstat GmbH, Berlin, Federal Republic of Germany

    P. Jähnig

  5. CNS Division, Novo Nordisk A/S, Soeborg, Denmark

    T. Honoré

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  1. P. -A. Löschmann
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  2. K. W. Lange
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  3. M. Kunow
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  4. K. -J. Rettig
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  7. L. Turski
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  9. P. Jenner
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  10. C. D. Marsden
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Löschmann, P.A., Lange, K.W., Kunow, M. et al. Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease. J Neural Transm Gen Sect 3, 203–213 (1991). https://doi.org/10.1007/BF02259538

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  • DOI: https://doi.org/10.1007/BF02259538

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