作者
Samantha C Salvage, Karthik H Chandrasekharan, Kamalan Jeevaratnam, Angela F Dulhunty, Andrew J Thompson, Antony P Jackson, Christopher L‐H Huang
发表日期
2018/4
来源
British journal of pharmacology
卷号
175
期号
8
页码范围
1260-1278
简介
Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca2+‐mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro‐arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization. These were studied in murine genetic models with modified Nav channel or intracellular ryanodine receptor (RyR2)‐Ca2+ channel function. Flecainide accesses its transmembrane Nav1.5 channel binding site during activated, open, states producing a use‐dependent antagonism. Closing either activation or inactivation gates traps flecainide within the pore. An early peak I …
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SC Salvage, KH Chandrasekharan, K Jeevaratnam… - British journal of pharmacology, 2018