Cardiovascular effects of indoramin in man--a dose ranging study.

Abstract

Abstract 1 The effect of single and repeated oral doses of indoramin 25 mg, 50 mg, 100 mg and placebo on arterial pressure and heart rate supine, standing and following immersion of the hand in ice was studied in five normal volunteers. 2 Each study period lasted 4 days. Observations were made before and at 2 and 4 after drug administration on days 1 and 4. On days 2 and 3, the drugs were administered daily, but no observations were made. 3 Indoramin did not change arterial pressure or heart rate in the supine position. 4 Indoramin did not reduce the cold pressor response. 5 Indoramin 25 mg produced small reductions in arterial pressure in the standing position, with no change in heart rate. 6 Indoramin 50 mg reduced systolic arterial pressure in the standing position on day 1 from 106.4 ± 2.6 mm Hg (mean ± s.e. mean) to 88.4 ± 7.4 mm Hg at 2 h (P < 0.05 when compared to placebo) and to 96.8 ± 2.2 mm Hg at 4 h (P < 0.05); diastolic pressure was reduced from 76.4 ± 4.1 mm Hg to 57.2 ± 6.4 mm Hg at 2 h (P < 0.01) and to 64.4 ± 4.3 mm Hg at 4 h (P < 0.05). The reductions in arterial pressure were accompanied by an increase in heart rate from 94.0 ± 4.5 beats min-1 to 102.0 ± 7.0 beats min-1 at 2 h, and to 104.6 ± 8.1 beats min-1 at 4 h (P < 0.05 when compared to placebo, but not when compared to the pre-treatment value). Similar changes were observed on day 4 after 50 mg indoramin, but the maximum reduction in arterial pressure was observed at 2 h on day 1, and 4 h on day 4. 7 Indoramin 100 mg reduced systolic arterial pressure in the standing position on day 1 from 114.0 ± 2.6 mm Hg to 99.2 ± 5.8 mm Hg at 2 h, and to 88.0 ± 5.9 mm Hg at 4 h (P < 0.01); diastolic pressure was reduced from 80.4 ± 3.4 mm Hg to 64.4 ± 3.2 mm Hg at 2 h (P < 0.05), and to 64.0 ± 4.5 mm Hg at 4 h (P < 0.05). The reduction in arterial pressure was accompanied by a small increase in heart rate from 102.2 ± 8.3 beats min-1 to 107.2 ± 12.7 beats min-1 at 2 h (P < 0.05 when compared to placebo, but not when compared to the pre-treatment value); no change in heart rate was observed at 4 h. The changes in arterial pressure and heart rate observed on day 4 after 100 mg indoramin were less than those observed on day 1, but these differences were not significant. 8 Indoramin reduces arterial pressure in normal man, but it is not possible to describe a dose-response relationship for the reduction. The reduction is accompanied by only a small increase in heart rate, possibly due to a direct bradycardic action of indoramin on the heart.