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

  • P. -A. Löschmann
  • K. W. Lange
  • M. Kunow
  • K. -J. Rettig
  • P. Jähnig
  • T. Honoré
  • L. Turski
  • H. Wachtel
  • P. Jenner
  • C. D. Marsden
Full Papers

DOI: 10.1007/BF02259538

Cite this article as:
Löschmann, P.A., Lange, K.W., Kunow, M. et al. J Neural Transm Gen Sect (1991) 3: 203. doi:10.1007/BF02259538

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.

Keywords

L-Dopa CPP NMDA antagonist NBQX AMPA antagonist MPTP common marmosets locomotor activity Parkinsonism 

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • P. -A. Löschmann
    • 2
  • K. W. Lange
    • 1
  • M. Kunow
    • 2
  • K. -J. Rettig
    • 2
  • P. Jähnig
    • 4
  • T. Honoré
    • 5
  • L. Turski
    • 2
  • H. Wachtel
    • 2
  • P. Jenner
    • 1
  • C. D. Marsden
    • 3
  1. 1.Parkinson's Disease Society Experimental Research Laboratories, Pharmacology GroupBiomedical Sciences Division, King's CollegeLondonUK
  2. 2.Research LaboratoriesSchering AGBerlinFederal Republic of Germany
  3. 3.University Department of Clinical Neurology, Institute of NeurologyThe National HospitalLondonUK
  4. 4.A F B Comstat GmbHBerlinFederal Republic of Germany
  5. 5.CNS DivisionNovo Nordisk A/SSoeborgDenmark
  6. 6.Department of NeuropsychopharmacologySchering AGFederal Republic of Germany

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