SR 33589, a new amiodarone-like antiarrhythmic agent: anti-adrenoceptor activity in anaesthetized and conscious dogs.
We have assessed the ability of amiodarone and the new amiodarone-like antiarrhythmic agent, SR 33589 (N,N-dibutyl-3-[4-((2-butyl-5-methylsulphonamido)benzofuran-3-yl-c arbonyl) phenoxy]propylamine), to inhibit the effects of adrenoceptor stimulation in anaesthetized and conscious dogs. In anaesthetized, atropinized dogs, adrenoceptor stimulation was achieved (i) by i.v. administration of adrenaline and measurement of increased blood pressure (ii) by i.v. administration of isoprenaline and measurement of increased heart rate and decreased blood pressure. In conscious dogs, adrenoceptor stimulation was achieved by i.v. administration of isoprenaline and measurement of increased heart rate. In anaesthetized, atropinized dogs, both amiodarone and SR 33589 inhibited to similar extents, alpha-adrenoceptor stimulation (as indicated by attenuation of adrenaline-induced increases in blood pressure). The beta 1-adrenoceptor inhibitory activity of SR 33589 (as demonstrated by blockade of isoprenaline-induced increases in heart rate) was significant, but less marked than amiodarone (heart rate elevation reduced by 39%, P < 0.001 with 10 mg/kg SR 33589 and by 52%, P < 0.01 with 10 mg/kg amiodarone). In contrast, its beta 2-adrenoceptor antagonistic activity (as demonstrated by blockade of isoprenaline-induced reduction in blood pressure) was more marked (mean blood pressure decrease reduced by 69%, P < 0.01 with 10 mg/kg SR 33589 and by 31%, P < 0.05 with 10 mg/kg amiodarone). In conscious dogs, both SR 33589 and amiodarone (12.5, 25 and 50 mg/kg p.o.) inhibited isoprenaline-induced increases in heart rate by approximately the same amount for varying durations depending on the dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Hodeige
D
D
Department of Pharmacology, Sanofi Research Centre, Brussels, Belgium.
Heyndrickx
J P
JP
Chatelain
P
P
Manning
A
A
D000284:Administration, Oral; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000638:Amiodarone / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D000077764:Dronedarone; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male
D018674:Adrenergic Antagonists; D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; D000077764:Dronedarone; D007545:Isoproterenol; D000638:Amiodarone