title: [New evolvement of antiarrhythmic drugs].
abstract: The Cardiac Arrhythmia Suppression Trial (CAST) casted serious doubts on the usefulness of Class I antiarrhythmic drugs, causing us to turn our attention from drugs impairing conduction of excitation in the myocardium by blocking sodium channels toward those producing increased refractoriness of myocardial cells by blocking potassium channels. This change in the direction of thinking from the "Na+ channel paradigm" to "K+ channel paradigm" resulted in the generation of newly synthetized Class III drugs that have the common electrophysiological property of suppressing outward K+ currents (IK, IK1, Ito) without affecting inward currents (INa, ICa). However, their reversed use-dependence of action potential duration prolonging effect contributes to their untoward action of proarrhythmias. It is still controversial if ion channel blockers acting solely on a certain kind of ion channels are more beneficial than drugs having compound actions such as amiodarone or sotalol. Molecular biology, if combined with arrhythmology, is expected to provide new chemical and pharmacological bases for creating novel antiarrhythmic drugs.
authors.affiliation: Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kanno
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D003864:Depression, Chemical; D015195:Drug Design; D006321:Heart / Q000187:drug effects; D006801:Humans; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D015222:Sodium Channels