SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF THE ANTIFIBRILLATORY EFFECT OF FLUORINATED DERIVATIVES OF CARAZOLOL AND CELIPROLOL - COMPARISONWITH PROPRANOLOL

1. The effects of carazolol, celiprolol and their respective fluorinat ed derivatives (FD) on electrical stimulation threshold (EST) and vent ricular fibrillation threshold (VFT) were compared with those of propr anolol and propranolol-FD in Langendorff-perfused rabbit hearts. 2. Ca razolol, carazolol-FD, propranolol and propranolol-FD produced signifi cant dose-dependent elevation of both EST and VFT at all tested concen tration levels. In contrast, celiprolol and celiprolol-FD did not prod uce a significant change in either threshold. 3. On a dosage basis, th e order of antifibrillatory potency of these compounds is: carazolol-F D > propranolol-FD > carazolol > propranolol > celiprolol-FD > celipro lol. 4. The results of this study seem to indicate the importance of m embrane stabilizing effect for a potent antifibrillatory action of bet a-adrenoceptor blocking agents. Furthermore, fluorination is demonstra ted to produce more potent antifibrillatory activity than that of the parent drugs.