Participation of central and peripheral κ₁ and κ₂ opioid receptors in arrhythmogenesis

1. The κ₁ and κ₂ opioid receptor agonists U-62066 (8 mg/kg, i.p.) and (-)-bremazocine (0.7mg/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 κ₁ opioid receptor agonists U-50 488 (110 nmol) and [D-Ala²]- dynorphin A (20 nmol) and the κ₂ 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 κ₁ 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.