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The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention.

Abstract
In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, including synaptic transmission, cerebral ischemia, epilepsy, brain trauma, and tissue inflammation. Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems. Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASIC1a activation in acidosis-mediated brain injury, small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke.
AuthorsTian-dong Leng, Zhi-gang Xiong
JournalActa pharmacologica Sinica (Acta Pharmacol Sin) Vol. 34 Issue 1 Pg. 33-8 (Jan 2013) ISSN: 1745-7254 [Electronic] United States
PMID22820909 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Acid Sensing Ion Channel Blockers
  • Acid Sensing Ion Channels
  • Small Molecule Libraries
Topics
  • Acid Sensing Ion Channel Blockers (chemistry, pharmacology)
  • Acid Sensing Ion Channels (metabolism)
  • Animals
  • Brain (drug effects, metabolism, pathology)
  • Humans
  • Small Molecule Libraries (chemistry, pharmacology)
  • Stroke (drug therapy, metabolism, pathology)

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