Differential blockade of alpha-adrenoceptors by indoramin

The effect of equihypotensive single oral doses of indoramin (mean dose 67 mg), phenoxybenzamine (mean dose 50 mg), hydralazine (mean dose 133 mg) and placebo on arterial pressure and heart rate in the supine and standing position was studied in six normal volunteers. Observations were made before and at 2 and 4 h after drug administration. Plasma noradrenaline (NA) was measured at each time interval in the supine position, and after 4 min of standing. Plasma renin activity (PRA) was measured at each time interval after 30 min in the standing position. The three active drugs reduced systolic arterial pressure in the standing position to a similar extent (indoramin, -24 mm Hg; phenoxybenzamine, -23.4 mm Hg; hydralazine, -30.4 mm Hg). The maximum effect of indoramin and phenoxybenzamine was observed at 4 h, and of hydralazine at 2 h after drug administration. The reductions of arterial pressure in the standing position were accompanied by increases in heart rate, plasma NA and PRA. Small increases were observed after indoramin (heart rate, + 9.2 beats min-1; plasma NA, + 126 pg/ml; PRA, + 0.33 ng angiotensin 1 ml-1 h-1), greater increases after phenoxybenzamine (heart rate, + 20; plasma NA, + 210; PRA, + 0.47), and the greatest i...Continue Reading