Effects of Platelet-Activating Factor Antagonists WEB 2086 and BN 50730 on Digoxin-Induced Arrhythmias


Author for correspondence: İclal Çakici, Department of Pharmacology, Faculty of Pharmacy, Gazi University, 06330 Hipodrom, Ankara, Turkey (fax + 90-312-2235018).

* Preliminary results of the present study were presented at the “Eurotox 93”, Uppsala, Sweden, June 30–July 3, 1993, and published as an abstract in Pharmacology & Toxicology 1993, 73, Suppl., p. 77 (p4/09).


Abstract: Effects of platelet-activating receptor antagonists WEB 2086 (1.0-30.0 mg · kg–1 intravenously) and BN 50730 (10.0 mg · kg–1 intravenously) alone or in combination with CGS 8515 (a specific 5-lipoxygenase inhibitor, 0.3 mg · kg–1 intravenously) and Dazmegrel® (a thromboxane synthase inhibitor, 1.0 mg · kg–1 · hr–1 intravenous infusion) on digoxin-induced arrhythmias were investigated in anaesthetised guinea-pigs. ECG, mean arterial blood pressure, heart rate and arrhythmias were recorded, starting 30 min. before digoxin administration and continuing for 60 min. afterwards. WEB 2086 (10.0 mg · kg–1 intravenously) reduced the mortality rate and arrhythmia score significantly compared to the control values. However, in combination with CGS 8515, it did not affect the mortality rate. BN 50730 (10.0 mg · kg–1) reduced the incidence of ventricular fibrillation and also arrhythmia score. BN 50730 in combination with Dazmegrel® was reduced the arrhythmia score, incidence of ventricular fibrillation and mortality rate significantly, compared to control values. Digoxin-induced acute rise in mean arterial blood pressure was not affected by any of drug treatment except WEB 2086 (10.0 mg · kg–1) in combination with CGS 8515. Heart rate values did not differ between groups. However, pressure-rate index was reduced by WEB 2086 alone or in combination with CGS 8615. Results showed that although two different platelet-activating factor antagonists have different effects on the incidence of ventricular fibrillation and mortality, they improved the digoxin-induced arrhythmias when they were used either separately or in combination with CGS 8515 or Dazmegrel® by implicating that platelet-activating factor has a role on digoxin-induced arrhythmias.