Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults

Academic Article

Abstract

  • Background: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral γ-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. Objective: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. Methods: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. Results: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). Conclusion: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.
  • Authors

    Published In

  • Neurology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Kuzniecky R; Ho S; Pan J; Martin R; Gilliam F; Faught E; Hetherington H
  • Start Page

  • 368
  • End Page

  • 372
  • Volume

  • 58
  • Issue

  • 3