Pregabalin exerts oppositional effects on different inhibitory circuits in human motor cortex: A double-blind, placebo-controlled transcranial magnetic stimulation study

Abstract

Purpose: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). Methods: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. Results: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 ± 7% of unconditioned response) compared with placebo (60 ± 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 ± 4% of unconditioned response) compared with placebo (45 ± 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 ± 8 ms or 145 ± 8 ms after placebo to 162 ± 7 ms or 161 ± 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. Conclusions: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest γ-aminobutyric acid (GABA)B-receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the α(2)-δ subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine. © 2006 International League Against Epilepsy.