Einfluss des Antiparkinsonmedikamentes Amantadin auf die Exzitabilität des menschlichen Motorkortex – Eine prospektive, placebokontrollierte, doppelblinde Studie
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Philipps-Universität Marburg
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Abstract
Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson’s disease (PD), and acute or chronic druginduced
dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism,
blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have
been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor
cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment
curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition
(L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS
paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake
of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo.
The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but
the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP,
or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The
decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic
circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect
on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning
and use-dependent plasticity.
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Dates
Created: 2007Issued: 2007-04-12Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Transkranielle MagnetstimulationExzitabilitätMotor cortex excitabilityGABATMSTranscranial magnetic stimulationAmantadineNMDA-RezeptorGlutamateGABA
DFG-subjects
Morbus ParkinsonNMDA-AntagonismusMotorkortexAmantadinNMDAGlutamat
DDC-Numbers
610
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John, Daniel (132733714): Einfluss des Antiparkinsonmedikamentes Amantadin auf die Exzitabilität des menschlichen Motorkortex – Eine prospektive, placebokontrollierte, doppelblinde Studie. : Philipps-Universität Marburg 2007-04-12. DOI: https://doi.org/10.17192/z2007.0201.
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This item has been published with the following license: In Copyright