A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers.
1. This study used a continuous-wave echo-Doppler method (Exerdrop) to investigate the effects of beta-adrenoceptor antagonism and partial agonism on cardiovascular responses at rest and during dynamic exercise. 2. A double-blind, randomised, placebo controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers; single oral doses of medication were administered at weekly intervals. Rest and exercise (supine bicycle) haemodynamics were assessed at 0, 2, 4, 6 and 8 h following dosing. 3. Before dosing and after placebo, the aortic flow velocity, acceleration and velocity integral increased progressively during exercise, as did heart rate, blood pressure and cardiac output. 4. Following metoprolol 50 mg, heart rate was significantly reduced without change in systolic or diastolic blood pressure. Echo-Doppler peak acceleration and velocity decreased at rest. On exercise, heart rate and systolic blood pressure fell significantly; the increase in acceleration was significantly blunted compared with placebo (a decrease of 15.2% at rest and 22.9% at 75 watts; P < 0.01 vs placebo). Peak velocity fell significantly by 75 watts exercise. 5. Celiprolol 200 mg at rest significantly increased systolic blood pressure, peak acceleration and velocity. On exercise celiprolol, in contrast to metoprolol, did not reduce peak acceleration or peak velocity; however exercise heart rate and systolic blood pressure were significantly reduced. The difference between celiprolol and metoprolol in respect of peak acceleration persisted over the 8 h of the study. 6. These differences between metoprolol and celiprolol are compatible with the partial agonism of celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Silke
B
B
University Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Thompson
A
A
Leitch
A
A
Riddell
J G
JG
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D017272:Celiprolol / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D015444:Exercise / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D012146:Rest
D000319:Adrenergic beta-Antagonists; D017272:Celiprolol; D008790:Metoprolol