The effects of drugs interacting with opioid receptors on the early ventricular arrhythmias arising from myocardial ischaemia

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Abstract
The effects of a range of opioid receptor agonists and antagonists with differing opioid receptor selectivities on ischaemia‐induced arrhythmias in anaesthetised rats was investigated. Naloxone was antiarrhythmic only at doses expected to antagonise κ‐ and δ‐receptors in addition to μ‐receptors. The opioid receptor antagonist Mr 2266, which is twice as potent at κ‐receptors as at μ‐receptors dose‐dependently reduced the incidence and severity of the arrhythmias resulting from coronary artery occlusion. The opioid receptor antagonist m 8008 (1 mg kg−1), which is twice as potent at δ‐receptors as at μ‐receptors but has very little affinity for the κ‐receptor, did not exhibit any beneficial antiarrhythmic properties. MrZ 2593, a quarternary complex of naloxone which does not readily cross the blood brain barrier, was antiarrhythmic which implies that the antiarrhythmic actions of opioid receptor antagonists may be mediated via peripheral opioid receptors. The agonists, diamorphine, [Leu] enkephalin and U‐50,488H exhibited no significant arrhythmogenic effects under the present experimental conditions. It is tentatively suggested that blockade of peripheral κ‐receptors during acute myocardial ischaemia may result in an antiarrhythmic effect.