1. The effects of single oral doses of three beta‐adrenoceptor partial agonists (Ro 31‐1118, flusoxolol and pindolol), two beta‐adrenoceptor antagonists (propranolol and atenolol), two beta‐adrenoceptor agonists (salbutamol and prenalterol) and placebo on sleeping heart rate, quality of sleep, supine heart rate, exercise heart rate, blood pressure, forearm blood flow and finger tremor were studied in eight healthy male volunteers. 2. Sleeping heart rate was increased by Ro 31‐ 1118, flusoxolol, pindolol, salbutamol and prenalterol and decreased by propranolol and atenolol. 3. None of the drugs studied affected quality of sleep. 4. Supine heart rate was increased by flusoxolol, prenalterol and salbutamol, unaffected by Ro 31‐1118 and pindolol and reduced by propranolol and atenolol. 5. Exercise heart rate was reduced by both beta‐adrenoceptor antagonists and the three partial agonists and unaffected by salbutamol and prenalterol. 6. Systolic blood pressure was increased by Ro 31‐1118, flusoxolol, salbutamol and prenalterol, unaffected by pindolol and reduced by propranolol and atenolol. Diastolic blood pressure was reduced by salbutamol and prenalterol. 7. Forearm blood flow was increased by Ro 31‐1118, salbutamol and prenalterol, unchanged by pindolol and flusoxolol and decreased by atenolol and propranolol. 8. Finger tremor was increased by Ro 31‐1118, flusoxolol, pindolol, salbutamol, and prenalterol. 9. beta‐adrenoceptor partial agonists have different effects on the cardiovascular system and finger tremor to beta‐adrenoceptor antagonists. 10. While Ro 31‐ 1118 and flusoxolol are antagonists mainly at the beta 1‐adrenoceptor they have agonist activity at both beta 1‐ and beta 2 adrenoceptors. 11. While pindolol is a non‐selective antagonist its agonist activity is mainly at the beta 2‐adrenoceptor.

Selectivity for beta 1- and beta 2-receptors to xamoterol, prenalterol and salbutamol were tested using ICI 118 551, a specific beta 2-receptor antagonist. Measurements were made of heart rate at rest and exercise, blood pressure, forearm blood flow and finger tremor. The actions of xamoterol were similar to those previously demonstrated, and were unaffected by beta 2-blockade, indicating selectivity for the beta 1-receptor. Salbutamol was selective for the beta 2-receptor and prenalterol was active at both.

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.

An automated system for the measurement of peripheral blood flow using venous occlusion plethysmography based on the low-cost Apple II microcomputer, together with purpose-built compressor unit and data acquisition interface, has been developed. The computer performs the dual role of controlling the timing of inflation and deflation of the occluding cuffs and recording the resulting increase in limb circumference. Ten 8 s epochs of data are acquired and analysed per session. Flow rate is computed using a least squares fit between 0.5 and 4.0 s after cuff inflation, giving on-line indication of blood flow. Venous capacitance and digital systolic pressure may be measured using additional algorithms. The system has been used for the investigation of circulatory disorders and in the assessment of drugs acting on the peripheral circulation.