title: Antiarrhythmic potential of drugs targeting the cardiac ryanodine receptor Ca2+ release channel: case study of dantrolene.
abstract: Driven by the limitations of the traditional antiarrhythmic pharmacology, current antiarrhythmic research is trying to identify new avenues for the development of specific and safe antiarrhythmic drugs. One of the most promising approaches in this field is the amelioration of the abnormal events in cellular Ca(2+) handling originating from the dysfunction of ryanodine receptor Ca(2+) release complex (RyR), which is an inevitable key factor in the pathology of myocardial dysfunction, remodeling and arrhythmogenesis. Accordingly, both in experimental and clinical situations, inhibition of abnormal activity of RyR, regardless of being the primary cause or a consequence during the pathogenesis appears to exert beneficial effect on disease outcome, including a marked antiarrhythmic defense. Considerable amount of our knowledge in this field originates from studies using dantrolene, a human drug with RyR stabilizing effect. Our review summarizes the cardiovascular pharmacology of dantrolene and the results of its use in experimental models of cardiac diseases, which emphasize a promising perspective for the possible antiarrhythmic application of RyR inhibition in the future.
authors.forename: Karoly
authors.initials: K
authors.lastname: Acsai
authors.forename: Norbert
authors.initials: N
authors.lastname: Nagy
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Marton
authors.forename: Kinga
authors.initials: K
authors.lastname: Oravecz
authors.affiliation: MTA-SZTE Cardiovascular Pharmacological Research Group, Dom ter 12. Szeged, 6720 Hungary. acsai.karoly@med.u-szeged.hu.
authors.forename: Andras
authors.initials: A
authors.lastname: Varro
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D019837:Ryanodine Receptor Calcium Release Channel; D003620:Dantrolene; D002118:Calcium