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Are NMDA antagonistic properties relevant for antiparkinsonianlike activity in rats?—Case of amantadine and memantine

  • W. Danysz
  • M. Gossel
  • W. Zajaczkowski
  • D. Dill
  • G. Quack
Full Papers

Summary

Amantadine (25, 50, 100 mg/kg), memantine (5, 10, 20 mg/kg) and MK-801 (0.05, 0.1, 0.2 mg/kg), all having NMDA channel blocking properties, were compared in three tests used for screening of antiparkinsonian agents in rats, namely: haloperidol-induced catalepsy, locomotor activity in monoamine depleted rats and rotation in rats with a unilateral substantia nigra lesion. Additionally, plasma levels of amantadine and memantine were assessed to gain an insight into the concentration ranges achieved at behaviorally active doses. Amantadine and (+)-MK-801 produced dosedependent inhibition of haloperidol-induced catalepsy while memantine was less efficacious producing clear-cut anticataleptic action at a dose of 10 mg/kg only but failing at 20 mg/kg due to myorelaxant activity. All agents attenuated sedation in monoamine depleted rats with amantadine being the least and MK-801 being the most effective. The same rank order of efficacy was seen in inducing ipsilateral rotations in rats after a substantia nigra lesion. On the basis of the present study and published data, it can be assumed that the doses of amantadine, memantine and MK-801 showing antiparkinsonian-like activity in animals result in plasma levels leading to NMDA antagonism. However, in the haloperidol-induced catalepsy test the efficacy of amantadine was higher than memantine, while the opposite was true for rotation and reserpine-induced sedation indicating pharmacodynamic differences between both agents.

Keywords

Catalepsy haloperidol locomotion reserpine α-methyl-ptyrosine rotation substantia nigra lesion amantadine memantine MK-801 NMDA receptor antagonism plasma levels brain levels 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • W. Danysz
    • 1
  • M. Gossel
    • 1
  • W. Zajaczkowski
    • 1
  • D. Dill
    • 1
  • G. Quack
    • 1
  1. 1.Departments of Pharmacology and Central AnalyticsMerz+CoFrankfurtFederal Republic of Germany

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