The glutamate antagonist Riluzole suppresses intracortical facilitation

Liepert, Joachim; Schwenkreis, Peter; Tegenthoff, Martin; Malin, J.‐P.

doi:10.1007/bf01294721

Cited by 249 publications

(143 citation statements)

References 21 publications

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“…It has been documented that the facilitation also depends on glutamate mechanisms, because the glutamate antagonist riluzole selectively suppresses the ICF (30). The reduction in early ICI without changes in ICF in our JME patients provides further evidence to support the hypothesis that inhibitory mechanisms may be altered in JME (19)(20)(21).…”

Section: Discussionsupporting

confidence: 65%

Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy

et al. 2000

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Summary: Purpose:We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy.Methods: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIS) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits.Results: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age-matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period.Conclusions: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.

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Section: Discussionsupporting

confidence: 65%

Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy

et al. 2000

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“…However, regarding the effects on motor cortex excitability there seems to be no difference between AMA and other NMDA receptor antagonists as determined by comparable changes of both ICF and ICI. The NMDA receptor antagonists dextromethorphan, memantine, and riluzole predominantly decrease ICF and to a lesser extent increase ICI (Liepert et al, 1997;Schwenkreis et al, 1999;Ziemann et al, 1998). The effect of riluzole and memantine negatively correlated with its plasma levels in case of ICF changes (Schwenkreis et al, 1999(Schwenkreis et al, , 2000.…”

Section: Effect Of Ama On Short Ici and Facilitationmentioning

confidence: 96%

“…Although ICI is in part regulated by GABA via postsynaptic GABA A -receptor activation (Kujirai et al, 1993), ICF is probably the more complex phenomenon in which more than one neurotransmitter (glutamate, dopamine, GABA) may be involved (Nakamura et al, 1997;Ziemann et al, 1996a). The application of antiglutamatergic drugs like riluzole, memantine, or dextromethorphan predominantly leads to a suppression of ICF (Liepert et al, 1997;Schwenkreis et al, 1999Schwenkreis et al, , 2000. This suppression isFto a lesser extentFalso present after application of GABAergic drugs such as vigabatrin, baclofen, or gabapentin (Ziemann et al, 1996a) or dopaminergic agents (Ziemann et al, 1997).…”

Section: Effect Of Ama On Short Ici and Facilitationmentioning

confidence: 99%

“…Furthermore, the influence of CNS-related drugs with a well-known mode of action was evaluated and differentiated from pathophysiological changes of the disease itself (Liepert et al, 1997;Ziemann et al, 1996a). Additionally, TMS has been used as a tool to characterize the in vivo effects of newly developed drugs on cortical excitability (Reis et al, 2002(Reis et al, , 2004Werhahn et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Human Motor Cortex Excitability by Single Doses of Amantadine

Reis

John

Heimeroth

et al. 2006

Neuropsychopharmacol

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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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“…Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF), and motor cortex indirect waves (I-waves) are studied by paired-pulse TMS. SICI is mainly influenced by glutamate and GABA A receptors and based on the induction of inhibitory postsynaptic potentials (Ziemann et al, 1996(Ziemann et al, , 1998aLiepert et al, 1997). ICF is thought to reflect activity of GABAergic and glutamatergic systems.…”

Section: Introductionmentioning

confidence: 99%