Topiramate Selectively Decreases Corticocortical Excitability in Human Motor Cortex - A Transcranial Magnetic Stimulation Study
Abstract number :
1.130
Submission category :
Year :
2001
Submission ID :
419
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
J. Reis, Dept. of Neurology, Philipps-University, Marburg, Germany; F. Tergau, M.D., Dept. of Neurophysiology, Georg-August-University, Göttingen, Germany; H.H. Mueller, Dept. of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany; H.
RATIONALE: Topiramate (TPM) is a novel drug with broad antiepileptic effect in focal and generalized epilepsies. In vitro studies suggest activity as activation-dependent sodium-channel blocker, as GABA-A-receptor agonist and as non-NMDA-glutamate receptor subtype antagonist. Transcranial magnetic stimulation (TMS) of the human brain allows to investigate the pharmacological effects of antiepileptic drugs on the excitability of motor corticospinal pathways. Using TMS we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability.
METHODS: In a double blind, placebocontrolled, crossover study design we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical stimulation induced silent period (CSP) and on corticocortical inhibition (CCI) and facilitation (CCF) in 20 healthy subjects using single and paired pulse TMS.
RESULTS: A significant dose-dependent increase of CCI was noted after a maximum of 200 mg TPM as compared to placebo at short interstimulus intervals (ISIs, 2 to 4 ms) and a dose-independent decrease on CCF was detected at longer ISIs (10 and 15 ms). A single oral dose up to 200 mg TPM had no effect on motor thresholds and motor evoked potential amplitudes during rest and voluntary muscle activation as well as the CSP.
CONCLUSIONS: We conclude that a single dose of TPM decreases human motor cortex excitability by selectively affecting corticocortical inhibition and to a lesser degree facilitation by GABA-A-ergic and/or glutamatergic mechanisms without significantly influencing measures depending on ion-channel associated membrane excitability or GABA-B-receptor activity.
Support: ULRAN-Foundation Professorship for Neurology/ Epileptology and Janssen-Cilag, Germany