Document Detail


Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats?--case of amantadine and memantine.
MedLine Citation:
PMID:  7710668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neural transmission. Parkinson's disease and dementia section     Volume:  7     ISSN:  0936-3076     ISO Abbreviation:  J Neural Transm Park Dis Dement Sect     Publication Date:  1994  
Date Detail:
Created Date:  1995-05-17     Completed Date:  1995-05-17     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8914371     Medline TA:  J Neural Transm Park Dis Dement Sect     Country:  AUSTRIA    
Other Details:
Languages:  eng     Pagination:  155-66     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Merz+Co, Frankfurt, Federal Republic of Germany.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
19982-08-2/Memantine; 6384-92-5/N-Methylaspartate; 768-94-5/Amantadine; 77086-22-7/Dizocilpine Maleate

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