title: Synthesis and pharmacological evaluation of the antifibrillatory effect of fluorinated derivatives of carazolol and celiprolol: comparison with propranolol.
abstract: 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.
authors.affiliation: Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
authors.forename: A A
authors.initials: AA
authors.lastname: Almotrefi
authors.forename: N
authors.initials: N
authors.lastname: Dzimiri
authors.forename: H Y
authors.initials: HY
authors.lastname: Aboul-Enein
authors.forename: L S
authors.initials: LS
authors.lastname: Premkumar
mesh_terms: 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
chemical_list: 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