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.
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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)
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Chemical References |
- N-Methylaspartate
- Dizocilpine Maleate
- Amantadine
- Memantine
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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
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