Atria-selective
antiarrhythmic drugs in need of alliance partners. Guideline-based treatment of
atrial fibrillation (AF) comprises prevention of
thromboembolism and
stroke, as well as antiarrhythmic
therapy by drugs, electrical rhythm conversion, ablation and
surgical procedures. Conventional
antiarrhythmic drugs are burdened with unwanted side effects including a propensity of triggering life-threatening
ventricular fibrillation. In order to solve this therapeutic dilemma, 'atria-selective'
antiarrhythmic drugs have been developed for the treatment of supraventricular arrhythmias. These drugs are designed to aim at atrial targets, taking advantage of differences in atrial and ventricular
ion channel expression and function. However it is not clear, whether such drugs are sufficiently antiarrhythmic or whether they are in need of an alliance partner for clinical efficacy. Atria-selective Na+ channel blockers display fast dissociation kinetics and high binding affinity to inactivated channels. Compounds targeting atria-selective K+ channels include blockers of ultra rapid delayed rectifier (Kv1.5) or
acetylcholine-activated
inward rectifier K+ channels (Kir3.x), inward rectifying K+ channels (Kir2.x),
Ca2+-activated K+ channels of small conductance (SK), weakly rectifying two-pore domain K+ channels (K2P), and
transient receptor potential channels (TRP). Despite good antiarrhythmic data from in-vitro and animal model experiments, clinical efficacy of atria-selective
antiarrhythmic drugs remains to be demonstrated. In the present review we will briefly summarize the novel compounds and their proposed antiarrhythmic action. In addition, we will discuss the evidence for putative improvement of antiarrhythmic efficacy and potency by addressing multiple pathophysiologically relevant targets as possible alliance partners.