title: Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura.
abstract: 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.
  
  
  CONCLUSIONS
  The observations here identify an entirely novel treatment strategy for migraine.
authors.affiliation: Headache Group, Department of Neurology, University of California at San Francisco, San Francisco, CA 94115, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Holland
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.forename: Anna P
authors.initials: AP
authors.lastname: Andreou
authors.forename: Nazia
authors.initials: N
authors.lastname: Karsan
authors.forename: John A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D062565:Acid Sensing Ion Channels / Q000187:drug effects* / Q000235:genetics; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020325:Migraine with Aura / Q000188:drug therapy* / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014276:Trigeminal Nerve / Q000187:drug effects
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D004232:Diuretics; D000584:Amiloride