Pharmacodynamic Comparison of<scp>l</scp>-Bunolol with Propranolol, Metoprolol, and Placebo

Twelve healthy volunteers received single oral doses of propranolol (80 mg), metoprolol (100 mg), L-bunolol (2 mg), and placebo in a four-way crossover study. Blood pressure, ventricular rate, and echocardiographically determined ejection fraction, ejection time, and mean rate of circumferential fiber shortening (mVcf) were measured before dosing and at multiple time points during 10 hours after each dose, with subjects maintained in the supine position. Reductions in systolic and diastolic blood pressure following administration of each of the beta blockers were greater than those observed with placebo, but differences among the four treatments were not significant. Heart rate reductions with the beta blockers differed significantly from placebo (P less than .001), but differences among the three beta blockers were not significant. Differences among the four treatments in mVcf decrement did not attain significance at the 5% level (.05 less than P less than .1), and there were no significant differences in ejection-time prolongation or ejection-fraction reduction. Thus, reduced blood pressure, heart rate slowing, and reduced cardiac contractility may be associated with placebo treatment and may indicate the need for placebo controls in studies of the cardiovascular effects of beta blockers. Despite differing secondary pharmacologic properties, the three beta blockers reduced heart rate to a similar extent. Other effects of the beta blockers on blood pressure and cardiac contractility could not be consistently distinguished from those associated with placebo.