[Specificity of the anti-arrhythmic effect of kappa1-opioid receptor agonists]

It is demonstrated that intravenous administration of the kappa 1-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 kappa-OR blocking with norbinaltorphimine. Preliminary administration of of a high-affinity kappa 1-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 kappa 1-OR agonists in the adrenal, ischemic, and reperfusion arrhythmia models has a receptor-specific character.