Antiarrhythmic and proarrhythmic properties of σ-receptor ligands

It has been found that the σ₁- and σ₃-receptor antagonists, DuP 734 intraperitoneally and XJ 448 intravenously, had antiarrhythmic effects against epinephrine-induced arrhythmias in rats. The ED₅₀ for antiarrhythmic effect of DuP 734 was 0.157 mg/kg after intraperitoneal administration. Other σ-receptor antagonists (rimcazole, BMY 14802, haloperidol) did not affect the incidence of epinephrine-induced arrhythmias. σ₁-Receptor agonists (DTG, N-allyl-normetazocine, (+)-3-PPP, (-)-3-PPP) had proarrhythmic effect after systemic administration. The σ-agonist N-allyl-normetazocine and σ-antagonist XJ 488 had no effect on the incidence of epinephrine-induced arrhythmias after intracerebroventricular administration. Therefore, it appears that the central nervous system does not play a significant role in the antiarrhythmic or proarrhythmic effects of σ-ligands. We hypothesize that these effects of σ-ligands might be dependent on their action on cardiac σ-receptors.