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

Abstract

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.

• Authors: W Danysz, M Gossel, W Zajaczkowski, D Dill, G Quack
• Journal: Journal 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
• PMID: 7710668 (Publication Type: Journal Article)

Chemical References

• N-Methylaspartate
• Dizocilpine Maleate
• Amantadine
• Memantine

Topics

• 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