KATP channel openers: structure-activity relationships and therapeutic potential

Med Res Rev. 2004 Mar;24(2):213-66. doi: 10.1002/med.10060.


ATP-sensitive potassium channels (K(ATP) channels) are heteromeric complexes of pore-forming inwardly rectifying potassium channel subunits and regulatory sulfonylurea receptor subunits. K(ATP) channels were identified in a variety of tissues including muscle cells, pancreatic beta-cells, and various neurons. They are regulated by the intracellular ATP/ADP ratio; ATP induces channel inhibition and MgADP induces channel opening. Functionally, K(ATP) channels provide a means of linking the electrical activity of a cell to its metabolic state. Shortening of the cardiac action potential, smooth muscle relaxation, inhibition of both insulin secretion, and neurotransmitter release are mediated via K(ATP) channels. Given their many physiological functions, K(ATP) channels represent promising drug targets. Sulfonylureas like glibenclamide block K(ATP) channels; they are used in the therapy of type 2 diabetes. Openers of K(ATP) channels (KCOs), for example, relax smooth muscle and induce hypotension. KCOs are chemically heterogeneous and include as different classes as the benzopyrans, cyanoguanidines, thioformamides, thiadiazines, and pyridyl nitrates. Examples for new chemical entities more recently developed as KCOs include cyclobutenediones, dihydropyridine related structures, and tertiary carbinols.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Diabetes Mellitus, Type 2 / drug therapy
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / therapeutic use*
  • Ion Channel Gating / drug effects
  • Potassium Channel Blockers / chemistry*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channel Blockers / therapeutic use
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Drug / drug effects*
  • Receptors, Drug / metabolism
  • Research
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Sulfonylurea Receptors


  • ATP-Binding Cassette Transporters
  • Hypoglycemic Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Adenosine Triphosphate