Effect of Amantadine on Human Motor Cortex Excitability as Measured by TMS

Introduction: Amantadine has been frequently used for therapy of Parkinson's disease and influenza. The exact mechanism of action remains unclear. In vitro data suggest its main mechanism of action is NMDA receptor antagonism leading to a reduction of intracortical excitation. Aims: The aim of this study was to investigate the acute effect of amantadine on human motor cortex excitability in healthy subjects by transcranial magnetic stimulation (TMS) to reflect its mechanism of action and to get information on other ways of cortical modulation in vivo. Methods: In a placebo-controlled double blind crossover study the effect of a single oral dose of 50mg and 100mg amantadine on motor cortex excitability of 14 healthy subjects was measured by TMS. Used paradigms were motor thresholds, MEP amplitude and recruitment curves, silent period, and – by double pulse TMS – intracortical inhibition ICI (interstimulus interval 2 and 3 ms), facilitation ICF (interstimulus interval 10 and 15 ms) and late inhibition at 150 ms interstimulus interval prior to and 90 minutes after oral drug ingestion. A peripheral effect was measured by F-waves and M-latency. For statistical analysis the Wilcoxon sign rank test with Bonferroni adjustment was performed. Results: 90min. after intake of 100mg amantadine a significant decrease of ICF was measured. Furthermore, late inhibition at 150 ms increased significantly. A trend towards an increased ICI at interstimulus interval of 3 ms was also detected. Other parameters remained unchanged. Amantadine did not lead to changes of peripheral excitability. Conclusions: The in vivo TMS data support the action as an NMDA receptor antagonist reflected by a decrease of ICF. Possibly GABAergic effects may also play a role in presynaptic modulation of glutamatergic excitability, which can be assumed by the increased ICI and increased late inhibition.