Microdialysis studies with amantadine and memantine on pharmacokinetics and effects on dopamine turnover.
Amantadine and memantine are in clinical use for the treatment of neurodegenerative diseases such as M. Parkinson and dementia syndrome. In order to contribute to the understanding of the interaction of these uncompetitive NMDA-antagonists with the dopaminergic system in the striatum, the pharmacokinetics and the effects of amantadine and memantine on the dopaminergic system were examined in a microdialysis study in anaesthetized rats. Both substances achieved extracellular fluid concentrations in the striatum known to block NMDA receptors, supporting the assumption that NMDA receptor antagonism is their primary mechanism of action. Both, memantine, and to a lesser degree, amantadine induce a modest dopamine overflow not paralleled by HVA or DOPAC. The small increase in dopamine overflow cannot add substantially to the drugs' action and may be generated indirectly via their NMDA-antagonistic properties.
Quack
G
G
Department of Pharmacology, Merz & Co. GmbH & Co., Frankfurt, Federal Republic of Germany.
Hesselink
M
M
Danysz
W
W
Spanagel
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000547:Amantadine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008559:Memantine / Q000493:pharmacokinetics / Q000494:pharmacology*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D000547:Amantadine; D004298:Dopamine; D008559:Memantine; D006719:Homovanillic Acid