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 an 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 Beta-
adrenoceptors. This is a novel pharmacological action warranting further investigation.U