Evaluation of the beta-adrenoceptor blocking activity of the Class Ic antiarrhythmic drug diprafenone in man.
The beta-adrenoceptor blocking activity of the new Class Ic-antiarrhythmic drug diprafenone has been determined in man in comparison with that of propranolol, using the standardized isoproterenol test. Following placebo, the dose of isoproterenol which increased the heart rate by 25 beats.min-1 (CD25) was 0.84 (0.1-2.72) micrograms (median and range). Two hours following single oral doses of 200 mg diprafenone (3.61 micrograms; 1.53-44.15) or 40 mg propranolol (16.06 micrograms; 9.15-27.04) significantly higher CD25-values were found. The affinity constants for the beta-adrenergic receptors calculated on the basis of free drug in the plasma were similar for propranolol and diprafenone (2.79 vs. 2.60 nM-1, respectively). Thus, diprafenone showed a definite degree of beta-blocking activity in a clinically relevant range of plasma concentrations.
Wagner
F
F
Abteilung für Klinische Pharmakologie, Benedikt Kreutz Rehabilitationszentrum, Bad Krozingen, Federal Republic of Germany.
Jähnchen
E
E
Trenk
D
D
D000319:Adrenergic beta-Antagonists; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D011405:Propafenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011897:Random Allocation
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; C047546:diprafenone; D011405:Propafenone; D011433:Propranolol; D007545:Isoproterenol