Differential Inhibition of Human Nav1.2 Resurgent and Persistent Sodium Currents by Cannabidiol and GS967

Int J Mol Sci. 2020 Apr 1;21(7):2454. doi: 10.3390/ijms21072454.


Many epilepsy patients are refractory to conventional antiepileptic drugs. Resurgent and persistent currents can be enhanced by epilepsy mutations in the Nav1.2 channel, but conventional antiepileptic drugs inhibit normal transient currents through these channels, along with aberrant resurgent and persistent currents that are enhanced by Nav1.2 epilepsy mutations. Pharmacotherapies that specifically target aberrant resurgent and/or persistent currents would likely have fewer unwanted side effects and be effective in many patients with refractory epilepsy. This study investigated the effects of cannbidiol (CBD) and GS967 (each at 1 μM) on transient, resurgent, and persistent currents in human embryonic kidney (HEK) cells stably expressing wild-type hNav1.2 channels. We found that CBD preferentially inhibits resurgent currents over transient currents in this paradigm; and that GS967 preferentially inhibits persistent currents over transient currents. Therefore, CBD and GS967 may represent a new class of more targeted and effective antiepileptic drugs.

Keywords: CBD; GS967; Nav1.2; Prax330; antiepileptic drugs; cannabidiol; persistent current; resurgent current; voltage-gated sodium channels.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Anticonvulsants / pharmacology
  • Cannabidiol / pharmacology*
  • Epilepsy / drug therapy
  • Epilepsy / genetics
  • Epilepsy / physiopathology
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / drug effects*
  • Ion Channel Gating / genetics
  • Ion Channel Gating / physiology
  • Mice
  • Mutation
  • NAV1.2 Voltage-Gated Sodium Channel / genetics
  • NAV1.2 Voltage-Gated Sodium Channel / physiology*
  • Neurons / drug effects
  • Neurons / physiology
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Pyridines / pharmacology*
  • Triazoles / pharmacology*


  • 6-(4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)(1,2,4)triazolo(4,3-a)pyridine
  • Anticonvulsants
  • NAV1.2 Voltage-Gated Sodium Channel
  • Protein Isoforms
  • Pyridines
  • Triazoles
  • Cannabidiol