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New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel
  1. Leslie A Rudzinski1,
  2. Naymeé J Vélez-Ruiz2,
  3. Evan R Gedzelman3,
  4. Elizabeth A Mauricio4,
  5. Jerry J Shih4,
  6. Ioannis Karakis3
  1. 1Department of Neurology, University of Florida College of Medicine, Gainesville, Florida, USA
  2. 2Department of Neurology, University of Miami, Miami, Florida, USA
  3. 3Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
  4. 4Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
  1. Correspondence to Dr Ioannis Karakis, Department of Neurology, Emory University School of Medicine, Faculty Office Building at Grady Campus, 49 Jesse Hill Jr. Drive SE, Office 335, Atlanta, GA 30303, USA; ioannis.karakis{at}


Ezogabine, clobazam, and perampanel are among the newest antiseizure drugs approved by the Food and Drug Administration between 2011 and 2012. Ezogabine and perampanel are approved for adjunctive treatment of partial epilepsy. Perampanel is also approved for adjunctive treatment of primary generalized tonic–clonic seizures. Ezogabine and perampanel have novel mechanisms of action. Ezogabine binds to voltage-gated potassium channels and increases the M-current thereby causing membrane hyperpolarization. Perampanel is a selective, non-competitive 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist, which reduces neuronal excitation. Clobazam has been used worldwide since the 1970s and is approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. Clobazam is the only 1,5-benzodiazepine currently in clinical use, which is less sedating than the commonly used 1,4-benzodiazepines. Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated efficacy and good tolerability of these 3 new antiepileptic drugs. These drugs represent a welcome addition to the armamentarium of practitioners, but it remains to be seen how they will affect the landscape of pharmacoresistant epilepsy.

  • Epilepsy

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