Modulation of potassium channels by antiarrhythmic and antihypertensive drugs.
Agents that modulate cardiac and smooth muscle K+ channels have stimulated considerable interest in recent years because of their therapeutic potential in a number of cardiovascular diseases. Foremost among these drugs are the so-called Class III antiarrhythmic agents, which act by prolonging cardiac action potentials, and K+ channel openers, which hyperpolarize and thereby relax smooth muscle cells. Many of the newly developed Class III antiarrhythmic agents probably act by specific block of one subtype of delayed rectifier K+ current, IKr, whereas other agents block more than one type of cardiac K+ current. Much controversy exists over the specific type of K+ channel (or channels) in smooth muscle that are activated by the K+ channel openers. Both groups of K+ channel modulators have great therapeutic promise, but the Class III antiarrhythmic agents may suffer from a side-effect that is directly linked to their specific mechanism of action.
Sanguinetti
M C
MC
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D010627:Phenethylamines; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; D013449:Sulfonamides; C063968:E 4031; C063533:dofetilide