| 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 |
Related Documents
:
|
12021828 - Phencyclidine supersensitivity in rats with neonatal dopamine loss. 7713358 - The sigma-selective ligand ne-100 attenuates the effect of phencyclidine in a rat divin... 22037638 - Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides ... 16814748 - Subchronic phencyclidine treatment decreases the number of dendritic spine synapses in ... 16811478 - Effects of a pre-shock stimulus on temporal control of behavior. 2426718 - Urinary monoamine metabolites as indices of mental stress in healthy males and females. |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The roles of neuromelanin, binding of metal ions, and oxidative cytotoxicity in the pathogenesis of ...
Next Document: Cerebrospinal monoamine metabolites and amino acid content in patients with parkinsonian syndrome an...