Cardiovascular effects of alinidine and propranolol alone and in combination with hydralazine in normal man.

The effect of single oral doses of alinidine 80 mg, propranolol 40 mg, hydralazine 50 mg, alinidine 80 mg combined with hydralazine 50 mg, propranolol 40 mg combined with hydralazine 50 mg, and placebo on arterial pressure and heart rate was studied in five normal volunteers in the supine and standing positions and during exercise. Observations were made before and at 1, 2, 3, 4 and 6 h after drug administration. Alinidine 80 mg and propranolol 40 mg significantly reduced heart rate in the supine position, and on exercise. The reductions in supine heart rate produced by alinidine and propranolol were not significantly different, but the maximum effect of alinidine on exercise heart rate was observed later than that of propranolol. Propranolol reduced heart rate in the standing position at all time intervals after drug administration, but alinidine reduced standing heart rate only at 6 h ( < 0.01 when compared to placebo). Hydralazine 50 mg increased supine heart rate by 8-10 beats min when compared to the pre-treatment value. These increases were significant ( < 0.05) when compared to the pre-treatment value, but not when compared to placebo. Hydralazine increased standing heart rate from 71.4 ± 6.5 to 90.0 ± 7.0 beats min ( < 0.05 when compared to placebo), but had no effect on exercise heart rate. The small increase in supine heart rate following hydralazine therapy was reduced by alinidine and propranolol, but only propranolol reduced the significant increase in standing heart rate produced by hydralazine. Hydralazine reduced diastolic arterial pressure in the supine position at 2 and 4 h after drug administration ( < 0.05 when compared to placebo), but had no effect on systolic or diastolic arterial pressure in the standing position or on exercise. Propranolol produced small reductions in systolic arterial pressure in the standing position, which were not significant when compared to placebo; diastolic pressure was unchanged. Propranolol reduced systolic pressure during exercise at 2, 4 and 6 h after drug administration ( < 0.05 when compared to placebo); diastolic pressure was unchanged. The effects of hydralazine and propranolol combined on arterial pressure in the standing position were similar to those observed after propranolol alone, but combined therapy produced a greater reduction in exercise systolic pressure, although these differences were not significant. Alinidine reduced systolic arterial pressure in the supine position at 3, 4 and 6 h after drug administration ( < 0.01) and diastolic pressure at 2 and 4 h ( < 0.05 when compared to placebo). Alinidine reduced systolic arterial pressure in the standing position at 3, 4 and 6 h after drug administration ( < 0.05) and diastolic pressure at 2 h ( < 0.01) and 6 h ( < 0.05 when compared to placebo). During exercise, alinidine produced a small reduction in systolic arterial pressure which was not significant, and a reduction in diastolic pressure at 1 h ( < 0.05 when compared to placebo). The effects of hydralazine and alinidine combined on arterial pressure were similar to those observed after alinidine alone. Hydralazine and alinidine combined produced a greater fall in systolic arterial pressure in the standing position than the changes observed after hydralazine alone; these differences were significant ( < 0.05) at 2, 3, 4 and 6 h after drug administration. However, the increase in heart rate after combined therapy was less than that observed after hydralazine alone, but these differences were not significant. This would suggest that alinidine may reduce the tachycardia produced by hydralazine. Combined therapy with hydralazine and alinidine was associated with a high incidence of side effects. Alinidine alone produced dry mouth and tiredness in some subjects and syncope in one. A linidine reduced heart rate and arterial pressure in normal man, and may therefore have a role in the treatment of hypertension, when used alone or in combination with vasodilator therapy.