Effects of selective receptor agonists and antagonists during myocardial ischaemia

Abstract

The antiarrhythmic activities of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid receptor antagonists for δ, κ and μ receptors, respectively, were examined during the 30 min following coronary artery occlusion anaesthetised rats. The haemodynamic and electrocardiographic effects of the opioid receptor agonists [D-Ala 2,D-Leu 5]enkephalin (DADLE) (relatively selective for δ receptors), ICI-204448 (κ) and glyol (μ) were also investigated over the 30–90 min post ligation period. When administered intravenously 5 min before ligation, M8008 (0.5 mg kg −1 and 2.5 mg kg −1 reduced the number of ventricular ectopic beats but had no effect on the incidence or duration of ventricular fibrillation. NBT and naltrexone were not antiarrhythmic at a dose of 0.5 mg kg −1 (a concentration at which both drugs block κ receptors) the number of ventricular ectopics beats, the incidence of ventricular fibrillation and mortality were all reduced. All of the opioid receptor agonists caused a transient decrease in heart rate and in arterial blood pressure but none exhibited an arrhythmogenic effect. These studies suggest that the δ and κ opioid receptor antagonists used may be antiarrhythmic as a result of blockade of the action of endogenously released peptides acting on these receptors or that they have a non-specific ‘direct’ antiarrhythmic action.