HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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.
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
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: