AI Article Synopsis
- Cardiac arrhythmias are a key focus in heart-related research, with many antiarrhythmic drugs available, yet clinical trials show serious side effects limit their effectiveness, particularly in reducing arrhythmia-related deaths.
- Amiodarone is known for its strong antiarrhythmic effects but has harmful side effects due to its chemical structure, prompting the need for safer alternatives.
- The study reports the creation of new antiarrhythmic compounds that combine Class I/B and Class III features, discovering GYKI-16638 as a promising candidate with effective antiarrhythmic properties and a better safety profile.
Article Abstract
Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.
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| http://dx.doi.org/10.2174/0929867043456232 | DOI Listing |
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