Flumazenil does not affect intracortical motor excitability in humans: a transcranial magnetic stimulation study

Objective: The motor cortex may be subject to tonic inhibitory drive. One inhibitory mechanism is supported by activity at benzodiazepine (BZP) receptors. In this study we investigate whether or not the BZP antagonist, flumazenil, increases cortical motor excitability in humans. Methods: Eight healthy subjects received a 1 mg intravenous (i.v.) loading dose of flumazenil followed by a 0.5 mg i.v. infusion over the next 30 min. Before, during, and 1 h after flumazenil infusion, we measured cortical motor excitability using transcranial magnetic stimulation (TMS). This included resting motor threshold (rMT), paired-pulse measurements of intracortical inhibition and facilitation (ICI and ICF), recruitment curve (RC), and silent period (SP). We also measured F response and compound muscle action potential (CMAP) with peripheral nerve stimulation. The study was carried out using a randomized, double-blind crossover design controlled with a saline infusion. Results: None of the measures of cortical or peripheral excitability were significantly affected by drug administration. Conclusions: Our findings suggest that flumazenil has no effect on cortical motor excitability in normal humans. Significance: There does not appear to be any tonic activity at benzodiazepine receptors in the normal resting human motor cortex.