Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura

Ann Neurol. 2012 Oct;72(4):559-63. doi: 10.1002/ana.23653.


Objective: Migraine with aura is a severe debilitating neurological disorder with few relatively specific therapeutic options.

Methods: We used amiloride, a blocker of epithelial sodium channels, to evaluate its pharmacological potential and explored the biology of a potential mechanism of action in well-established experimental models.

Results: Amiloride was shown to block cortical spreading depression, the experimental correlate of aura, and inhibited trigeminal activation in in vivo migraine models, via an acid-sensing ion channel 1 mechanism. Remarkably, amiloride then demonstrated good clinical efficacy in a small open-labeled pilot study of patients, reducing aura and headache symptoms in 4 of 7 patients with otherwise intractable aura.

Interpretation: The observations here identify an entirely novel treatment strategy for migraine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / drug effects*
  • Acid Sensing Ion Channels / genetics
  • Adult
  • Amiloride / pharmacology
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebrovascular Circulation
  • Cortical Spreading Depression / drug effects
  • Diuretics / pharmacology
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Migraine with Aura / drug therapy*
  • Migraine with Aura / metabolism*
  • Nociceptors / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Trigeminal Nerve / drug effects


  • ASIC1 protein, mouse
  • Acid Sensing Ion Channels
  • Asic1 protein, rat
  • Diuretics
  • Amiloride