Synthesis and pharmacological evaluation of the antifibrillatory effect of fluorinated derivatives of carazolol and celiprolol: comparison with propranolol.
1. The effects of carazolol, celiprolol and their respective fluorinated derivatives (FD) on electrical stimulation threshold (EST) and ventricular fibrillation threshold (VFT) were compared with those of propranolol and propranolol-FD in Langendorff-perfused rabbit hearts. 2. Carazolol, carazolol-FD, propranolol and propranolol-FD produced significant dose-dependent elevation of both EST and VFT at all tested concentration levels. In contrast, celiprolol and celiprolol-FD did not produce a significant change in either threshold. 3. On a dosage basis, the order of antifibrillatory potency of these compounds is: carazolol-FD > propranolol-FD > carazolol > propranolol > celiprolol-FD > celiprolol. 4. The results of this study seem to indicate the importance of membrane stabilizing effect for a potent antifibrillatory action of beta-adrenoceptor blocking agents. Furthermore, fluorination is demonstrated to produce more potent antifibrillatory activity than that of the parent drugs.
Almotrefi
A A
AA
Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
Dzimiri
N
N
Aboul-Enein
H Y
HY
Premkumar
L S
LS
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D017272:Celiprolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000503:physiopathology; D005466:Fluorocarbons
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D017272:Celiprolol; D011433:Propranolol; C082959:carazolol FD; D005466:Fluorocarbons; C082960:celiprolol FD; C082961:propranolol FD