Evaluation of the antifibrillatory activity of fluorinated derivatives of indenolol and nadolol in isolated rabbit and rat hearts: comparison with propranolol.

The effects of indenolol and nadolol and of their respective fluorinated derivatives on ventricular fibrillation threshold were compared with propranolol in Langendorff-perfused rabbit hearts. Their effects on aconitine-induced ventricular tachycardia and fibrillation were also evaluated in Langendorff-perfused rat hearts. Propranolol, indenolol and indenolol fluorinated derivative produced significant dose-dependent increases in ventricular fibrillation threshold at all tested concentration levels. These compounds have also caused significant increases in the amount of aconitine required to produce ventricular tachycardia and fibrillation. Nadolol and nadolol fluorinated derivative did not produce any significant changes in the above-mentioned parameters except a small, but statistically significant, increase in ventricular fibrillation threshold produced by the highest concentration (2.64 microM) tested of nadolol fluorinated derivative. On a dosage basis, the order of potency of these compounds is indenolol fluorinated derivative greater than propranolol greater than indenolol greater than nadolol fluorinated derivative greater than nadolol. These results suggest that additional properties of beta-adrenergic blockers, such as membrane-stabilizing effects, may contribute to their antifibrillatory activity and that fluorination may tend to increase it.