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 increases after hydralazine (heart rate, + 26; plasma NA, + 250; PRA, + 1.16). In the supine position, indoramin and phenoxybenzamine produced no effect on arterial pressure, heart rate or plasma NA. Hydralazine produced small reductions in diastolic pressure, which were accompanied by an increase in heart rate of 25.5 beats min-1 (P less than 0.01 when compared to placebo) and in plasma NA of 223 pg ml-1 (P less than 0.05). Plasma NA, PRA and heart rate increased together and may be regarded as three interdependent indices of sympathetic activity. Indoramin reduced the degree of increase of plasma NA, PRA and heart rate per unit fall in pressure, when compared to phenoxybenzamine and hydralazine. The effect of phenoxybenzamine and hydralazine on the degree of increase was similar. The results are consistent with the hypothesis that indoramin produces selective postsynaptic alpha 1-adrenoceptor blockade in man, and therefore produces relatively less tachycardia and NA increase than does a non-selective alpha-adrenoceptor antagonist (phenoxybenzamine) or an arteriolar vasodilator (hydralazine).

RCT Entities:   Population Interventions Outcomes