About specificity of the antiarrhythmic effect of κ₁-opioid receptor agonists

It is demonstrated that intravenous administration of the κ₁-opioid receptor (OR) agonists (-)-trans-(1S,S)-U-50,488 and (+)-trans-(1R,2R)-U-50,488 increases heart tolerance to the arrhythmogenic effect of epinephrine in rats. This antiarrhythmic effect was completely abolished by preliminary κ-OR blocking with norbinaltorphimine. Preliminary administration of of a high-affinity κ₁-OR agonist (-)-trans-(1S,S)-U-50,488 significantly reduced the incidence of ventricular arrhythmias upon coronary artery occlusion and reperfusion in vivo. The low-affinity (+)-trans-(1R,2R)-U-50,488 does not show antiarrhythmic activity under ischemia and reperfusion of myocardium. It is concluded that the antiarrhythmic action of κ₁-OR agonists in the adrenal, ischemic, and reperfusion arrhythmia models has a receptor-specific character.