Participation Of Central and Peripheral κ 1 and κ 2 Opioid Receptors In Arrhythmogenesis

SUMMARY 1. The κ 1 and κ 2 opioid receptor agonists U‐62066 (8 mg/kg, i.p.) and (–)‐bremazocine (0.7 mg/kg, i.v.), respectively, both exhibit anti‐arrhythmic properties against adrenaline‐induced dysrhythmias in rats. 2. In contrast, (+)‐bremazocine has no effect on adrenaline‐induced dysrhythmias. 3. The κ 1 opioid receptor agonists U‐50 488 (110 nmol) and [ D ‐Ala 2 ]‐dynorphin A (20 nmol) and the κ 2 opioid receptor agonist (–)‐bremazocine (30 nmol) exhibit pro‐arrhythmic properties following intracerebroventricular administration. 4. Prior administration of the κ opioid receptor antagonist nor‐binaltorphimine doses i.c.v. (14 nmol), i.p. (10 mg/kg), completely abolishes the pro‐arrhythmic (BNI, i.c.v., 14 nmol) as well as anti‐arrhythmic (BNI, 10 mg/kg, i.p.) effects of the κ opioid receptor agonists. 5. Neither hexamethonium (10 mg/kg, i.v.) nor atropine (1 mg/kg, i.v.) have any effect on the anti‐arrhythmic actions of the κ 1 opioid receptor agonist U‐62066 following systemic administration. 6. It is suggested that the anti‐arrhythmic effects of U‐62066 and (–)‐bremazocine are associated with the activation of peripheral κ opioid receptors and do not depend on the activation of κ opioid receptors in the autonomic nervous system.