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 Ca2+ handling originating from the dysfunction of ryanodine receptor Ca2+ 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.
Keywords: Dantrolene, ryanodine-receptor, Ca2+ release, delayed after-depolarization, arrhythmia.
Current Pharmaceutical Design
Title:Antiarrhythmic Potential of Drugs Targeting the Cardiac Ryanodine Receptor Ca2+ Release Channel: Case Study of Dantrolene
Volume: 21 Issue: 8
Author(s): Karoly Acsai, Norbert Nagy, Zoltan Marton, Kinga Oravecz and Andras Varro
Affiliation:
Keywords: Dantrolene, ryanodine-receptor, Ca2+ release, delayed after-depolarization, arrhythmia.
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 Ca2+ handling originating from the dysfunction of ryanodine receptor Ca2+ 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.
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Cite this article as:
Acsai Karoly, Nagy Norbert, Marton Zoltan, Oravecz Kinga and Varro Andras, Antiarrhythmic Potential of Drugs Targeting the Cardiac Ryanodine Receptor Ca2+ Release Channel: Case Study of Dantrolene, Current Pharmaceutical Design 2015; 21 (8) . https://dx.doi.org/10.2174/1381612820666141029103442
DOI https://dx.doi.org/10.2174/1381612820666141029103442 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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