Contrasting actions of celiprolol and metoprolol on cardiac performance in normal volunteers.
A double-blind, randomized, placebo-controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers. Rest and exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours following single oral doses of medication administered at weekly intervals. The influence of the ancillary pharmacological properties of metoprolol and celiprolol on cardiac pumping indices was assessed from heart rate and peak aortic acceleration (pkA-Exerdop). Following placebo, the heart rate and pkA increased progressively with exercise duration and workload. Following metoprolol 50 mg, the heart rate (-9.7 beat/min at 75 watts exercise) and pkA decreased. The blunting of acceleration was greater at higher exercise workloads (-6.7 m/sec2 at 75 watts exercise). Celiprolol reduced heart rate (-6.9 beat/min at 75 watts exercise) without a change in pkA. The heart rate/pkA relationship showed significant parallel displacement, downwards after metoprolol but upwards after celiprolol. Thus, for a given heart rate increment there was a greater decrease in pkA after metoprolol compared with celiprolol. The different ancillary pharmacological profiles of metoprolol and celiprolol resulted in contrasting hemodynamic profiles. The observed differences in the heart rate/pkA relationships may be attributable to the peripheral actions of these agents. The therapeutic relevance of the better maintained cardiac pumping indices on celiprolol for ischemic patients with impaired cardiac function warrants further investigation.
Silke
B
B
University Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Thompson
A
A
Riddell
J G
JG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D017272:Celiprolol / Q000494:pharmacology*; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D012016:Reference Values
D000319:Adrenergic beta-Antagonists; D017272:Celiprolol; D008790:Metoprolol