Effect of indoramin, labetalol and alinidine on sympathetic function in normal man.

Abstract

1 The effects of single oral doses of indoramin (mean dose 58 mg), labetalol (mean dose 150 mg), alinidine 80 mg and placebo on arterial pressure and heart rate in the supine and standing positions were studied in six normal volunteers. Doses were chosen to give equivalent reductions of arterial pressure in the standing position. Observations were made before and at 2 and 4 h after drug administration.2 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. 3 In the supine position, alinidine produced a significant reduction of systolic arterial pressure from 124.0 + 3.0 mm Hg to 104.3 + 4.1 mm Hg at 2 h (P < 0.01) and to 101.7 ± 2.2 mm Hg at 4 h (P < 0.01). Diastolic pressure was reduced from 74.7 ± 2.6 mm Hg to 57.0 + 4.6 mm Hg at 4 h (P < 0.01). Arterial pressure was unchanged after indoramin or labetalol administration. 4 In the supine position, heart rate was unchanged after indoramin, and small reductions were observed after labetalol and alinidine. Indoramin produced a significant increase in plasma NA. A small increase of plasma NA was observed after labetalol, and a small decrease after alinidine. 5 In the standing position, the three active drugs reduced systolic arterial pressure to a similar extent (indoramin, -26.7 mm Hg at 4 h after drug administration; labetalol, -21.3 mm Hg at 2 h; alinidine, -21.7 mm Hg at 4 h). 6 In the standing position, heart rate was increased by indoramin (+6.6 beats min-' at the time of maximum arterial pressure reduction) but reduced by labetalol (-10.4 beats min-') and alinidine (-7.6 beats min-). Plasma NA was increased after indoramin and labetalol (+ 191 and + 137 pg ml-1 respectively) but a small reduction was observed after alinidine (-128 pg ml-'). PRA was unchanged after labetalol. A small increase of PRA was observed after indoramin, and a significant increase after alinidine administration (1.29 ± 0.16 to 2.32 + 0.44 ng angiotensin I ml-' h-1 at 2 h, P < 0.05). 7 The effects of indoramin and labetalol may be correlated with their known pharmacological properties. Alinidine produced small reductions of heart rate and plasma NA, and an increase of PRA. The mechanism of the hypotensive action of alinidine is unknown, but these results suggest the possibility that reduction of sympathetic activity may be a component of this action.

Cutaneous arterial and venous alpha receptor blocking activity following intraduodenal indoramin to dogs

“…In contrast, prazosin caused a dose-related decrease in MAP and perfusion pressure in normotensive, anesthetized dogs. Blood pressure lowering by prazosin and by indoramin is due solely to a decrease in total peripheral resistance, as cardiac index increases slightly after 01 ,-adrenoceptor blockade [Baum et al, 1973;Baum and Shropshire, 1975;Coltart, 1981;Nicholls et al, 1981Nicholls et al, , 1983Nicholls et al, , 1984aGraham and Pettinger, 1979;Scriabine, 19801. Indoramin had no effect on HR, whereas prazosin increased HR in a dose related manner.…”

“…Indoramin is pharmacologically similar to prazosin in its mechanism of action (selective a , adrenoceptor antagonism). However, indoramin does not produce reflex tachycardia, first dose syncope, or orthostatic hypotension following acute or chronic administration for hypertension [Nicholls et al, 1983[Nicholls et al, , 1984a.…”

“…Indoramin is a selective, competitive, postsynaptic a 1 adrenoceptor antagonist [Alps et al, 1972al which effectively lowers systemic arterial pressure in anesthetized cats, dogs, and rats [Alps et al, 1972b;Baum et al, 1973;Baum and Shropshire, 19751 and in normal and hypertensive man [Coleman et al, 1979;Coltart, 1981;Nicholls et al, 1981Nicholls et al, , 1983Nicholls et al, , 1984a. Indoramin is pharmacologically similar to prazosin in its mechanism of action (selective a , adrenoceptor antagonism).…”

Indoramin in heart failure: Possible adverse effects on hemodynamics and exercise capacity

“…Pulmonary wedge pressure could also have risen again as a result of the peripheral vasoconstriction and increased afterload since changes in left ventricular filling pressure vary directly with changes in afterload in the presence of left ventricular failure.26 Finally, the observed fall in cardiac output could be a result of depression of left ventricular function as a result of indoramin's antiadrenergic activity. 25 Other antiadrenergic agents such as P-blocking drugs and clonidine may depress left ventricular function in the presence of heart failure despite reducing afterload. "…”