Studies of the agonist and antagonist activity of cicloprolol in man.

Abstract

To assess the partial agonist activity of cicloprolol in man, four studies were carried out in normal male volunteers. I and II. Open dose escalating studies of the effects of oral doses of the drug on exercise tachycardia and sleeping heart rate. III and IV. Double-blind randomized studies of the effects of placebo, cicloprolol 25 mg, cicloprolol 50 mg, cicloprolol 100 mg, atenolol 50 mg, pindolol 10 mg, salbutamol 8 mg and prenalterol 50 mg on sleeping heart rate, resting supine heart rate, blood pressure, forearm blood flow, finger tremor and exercise tachycardia. All doses of cicloprolol above 2.5 mg reduced an exercise tachycardia but there was no increase in effect above a dose of 50 mg. Cicloprolol caused a dose dependent increase in sleeping heart rate up to 200 mg. Cicloprolol increased resting supine heart rate, systolic blood pressure, forearm blood flow and finger tremor. None of the drugs affected quality of sleep. Cicloprolol has significant partial agonist activity at the beta 1-adrenoceptor as indicated by increases in heart rate and systolic blood pressure. The increases in finger tremor and forearm blood flow suggest that cicloprolol has some partial agonist activity at the beta 2-adrenoceptor.