Effects of Alinidine, A Novel Bradycardie Agent, on Heart Rate and Blood Pressure in Man
The effects of the oral administration of alinidine (ST567) were studied on heart rate and blood pressure in healthy subjects in the supine and standing positions and on an exercise tachycardia. Exercise tachycardia was reduced by the three doses (20, 40, and 80 mg) of alinidine, and supine and standing heart rate by 80 mg alinidine. The maximum reductions in heart rate occurred at 1 to 2 h but were still present at 6 h. Systolic and diastolic pressure in the supine and standing positions was significantly reduced by alinidine, 80 mg. A comparison of the effects of placebo, alinidine (80 mg), propranolol, (40 mg), and clonidine (0.1 mg) showed that the effects of alinidine on heart rate and blood pressure in the supine and standing positions and after exercise were similar to those of propranolol; clonidine had little effect on these parameters. Alinidine, 40 and 80 mg, had no effect on an isoprenaline tachycardia, which was competitively antagonised by propranolol, 40 mg. The oral administration of alinidine, 40 mg once daily and 40 mg twice daily, for 8 days reduced heart rate in supine and standing positions and on exercise tachycardia with small reductions in systolic and diastolic pressure. The effect of the twice-daily regimen was greater. Some subjects had a dry mouth after alinidine, and 8–9 h after 80 mg all subjects felt drowsy and sleepy. Tiredness was reported during the first 2 days of the chronic-dosing study. One subject had a visual disturbance after 40 mg. These studies show that alinidine reduces heart rate in man without blocking β-adrenoceptors. This is a novel pharmacological action warranting further investigation.