Effect of celiprolol, a new beta 1-alpha 2 blocker, on the cardiovascular response to exercise.

The pharmacodynamics of beta blockade with single oral doses of celiprolol 200 and 400 mg, compared with placebo, atenolol 50 and 100 mg, propranolol 80 and 160 mg, metoprolol 100 and 200 mg, and pindolol 5 and 10 mg, were evaluated in an open, incomplete-block study design employing 11 healthy male volunteers. Each subject received five of the 11 possible treatments at weekly intervals. The maximal rate-pressure product (RPP) induced by standardized treadmill exercise was measured 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after each treatment. During the course of the exercise test, heart rate and systolic blood pressure were recorded at one-minute intervals for five minutes. The maximal RPP, heart rate, and the maximum change from baseline were calculated for each exercise period. The data were analyzed using absolute reduction and percentage reduction of these parameters. All of the beta blockers tested produced significant decreases (P less than .05) in the exercise RPP, ranging from 16% reduction for celiprolol 200 mg to 47% reduction for propranolol 160 mg at peak response. Celiprolol 400 mg reduced the RPP by 31% at peak effect and did not differ significantly from the other treatments. Celiprolol 400 mg and atenolol 100 mg were the only agents that significantly reduced the RPP 24 hours posttreatment (20.7% and 21.7%, respectively) compared with placebo. Celiprolol 400 mg was the only agent to significantly reduce exercise heart rate 24 hours posttreatment (26.6 beats, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)