Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats?--case of amantadine and memantine.

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 dose-dependent 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.
AuthorsW Danysz, M Gossel, W Zajaczkowski, D Dill, G Quack
JournalJournal of neural transmission. Parkinson's disease and dementia section (J Neural Transm Park Dis Dement Sect) Vol. 7 Issue 3 Pg. 155-66 ( 1994) ISSN: 0936-3076 [Print] AUSTRIA
PMID7710668 (Publication Type: Journal Article)
Chemical References
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Amantadine
  • Memantine
  • Amantadine (blood, pharmacology)
  • Animals
  • Catalepsy (chemically induced)
  • Dizocilpine Maleate (pharmacology)
  • Locomotion (drug effects)
  • Male
  • Memantine (blood, pharmacology)
  • N-Methylaspartate (antagonists & inhibitors)
  • Rats
  • Rats, Sprague-Dawley
  • Rotation
  • Substantia Nigra

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