Investigations to characterize the antiarrhythmic action of bergamottine, a furocoumarin isolated from bergamot oil

Abstract

Bergamottine is a furocoumarin isolated from the non-volatile essential oil of Citrus bergamia Risso (Bergamot, Rutaceae) with antiarrhythmic properties. We investigated and classified its mechanism of action according to Vaughan Williams. We have found that bergamottine at a concentration range of 5-20 μg/mL (14.7-59 μM) decreased the frequency and the force of the contraction in spontaneously beating guinea-pig right atria and electrically paced left atria in a concentration-dependent manner. Furthermore this furocoumarin caused a parallel shift of the dose-response curve to CaCl 2 similar to that of verapamil in the electrically driven left atrium, indicating a possible Ca-antagonistic property. Bergamottine (1 mg/kg i.v.) significantly prolonged the atrioventricular conduction time, the corrected sinus-node recovery time and the corrected sinus-atrial conduction time in anaesthetized rabbits. Bergamottine did not inhibit isoprenaline-induced positive chronotropic responses in atrial muscle, indicating that it has no β-blocking activity, and did not show significant local-anaesthetic property in the guinea-pig intradermal wheal test. These results demonstrate that bergamottine seems to be an antiarrhythmic drug having class IV (inhibitor of calcium transport) type activity.