Effects Of Indoramin Research Articles

Prokinetic Effect of Indoramin, an Alpha Adrenergic Antagonist, on Gall Bladder Motility in Subjects with Gall Stone Disease

Prokinetic Effect of Indoramin, an Alpha Adrenergic Antagonist, on Gall Bladder Motility in Subjects with Gall Stone Disease

Antiarrhythmic and Metabolic Effects of Indoramin During Acute Regional Ischemia and Reperfusion in Isolated Rat Heart

The antiarrhythmic effect of alpha 1-adrenoceptor antagonists during myocardial ischemia and reperfusion remains controversial. The potential antiarrhythmic properties of indoramin, an alpha 1-antagonist, were assessed in the isolated perfused rat heart during regional ischemia and during sustained reperfusion. Coronary artery ligation (CAL) decreased the ventricular fibrillation threshold (VFT) of control hearts from 9.1 +/- 1.3 (pre-CAL, mean +/- SEM) to 2.1 +/- 0.5 mA 15 min post-CAL (p less than 0.0001). Perfusion with indoramin 10(-8) M (alpha 1-receptor antagonistic concentration) started 5 min prior to CAL did not prevent the fall in VFT after CAL. Indoramin 10(-6) M prevented the fall in VFT after CAL relative to the control group. Indoramin 10(-5) M markedly increased the VFT before CAL from 9.9 +/- 1.0 to 28.6 +/- 2.9 mA (p less than 0.0001) and prevented the fall in VFT after CAL. During reperfusion, indoramin 10(-5) M decreased the incidence of spontaneous ventricular fibrillation (VF) to 1 of 6 vs. 6 of 6 in the control group (p less than 0.02). Indoramin 10(-5) M preserved adenosine triphosphate in the reperfused myocardium: 2.82 +/- 0.06 vs. 2.16 +/- 0.21 mumol/g in the control group (p less than 0.05). Specific alpha 1-antagonist properties of indoramin did not appear to be involved in the antiarrhythmic effects.

Pre- and Postsynaptic Effects of Indoramin on Sympathetic Neuroeffector Transmission in Rabbit Aorta and Pulmonary Artery

The effects of indoramin on sympathetic neuroeffector transmission in rabbit isolated blood vessels were examined. Indoramin reduced the contractions of pulmonary artery evoked by electrical-field stimulation. The IC50 was 7.4 X 10(-8) M. In the presence of cocaine + corticosterone + propranolol, the IC50 was 5 X 10(-7) M. Amphetamine did not antagonize the steady-state inhibition caused by indoramin. Indoramin caused a slight enhancement of the field-stimulation-evoked 3H-overflow from pulmonary artery preloaded with 3H-noradrenaline. In the presence of cocaine + corticosterone + propranolol, indoramin also enhanced the stimulation-evoked 3H-overflow slightly. The effect of indoramin on stimulation-evoked 3H-overflow depended only slightly on stimulation frequencies (1-30 Hz): small enhancement at 1 Hz and nonsignificant changes at 3-30 Hz. Pretreatment with indoramin did not attenuate the inhibitory effect of clonidine on the stimulation-evoked 3H-overflow seen with bretylium. Indoramin and desmethylimipramine reduced the 3H-accumulation by aorta preloaded with 3H-noradrenaline. The IC50 was 3 X 10(-5)M (indoramin) and 10(-8)M (desmethylimipramine). Indoramin inhibited the contractions of aorta evoked by noradrenaline, phenylephrine, histamine and serotonin in a competitive manner. The corresponding pA2 values were 7.54, 7.98, 7.45, and 6.61. Indoramin decreased the maximal contractions of rabbit aorta evoked by potassium. These results suggest that indoramin is a potent competitive antagonist of postsynaptic alpha 1-adrenoceptors, while it may only have a slight inhibitory effect on presynaptic alpha 2-adrenoceptors. Indoramin is devoid of bretylium-like adrenergic neurone blocking activity, while it may act as reserpine. It is a weak inhibitor of the uptake-1 mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Hemodynamic and Hormonal Effects of Central Versus Peripheral Sympathetic Inhibition in Patients with Congestive Heart Failure

Indoramin, an alpha 1 antagonist, and guanabenz, an alpha 2 agonist, were given to 10 patients with severe congestive heart failure to compare the hemodynamic and hormonal effects of a reduction in sympathetic tone obtained through inhibition of postsynaptic alpha 1 receptors versus the decrease in sympathetic activity achieved by stimulating central or presynaptic peripheral alpha 2 adrenoceptors. Both drugs produced similar reduction in systemic arterial pressure. However, only indoramin significantly decreased systemic and pulmonary vascular resistances from 1529 +/- 526 to 1071 +/- 356 and from 721 +/- 422 to 412 +/- 257 dynes X s X cm-5, respectively, and increased stroke index from 26.6 +/- 9.5 to 33.3 +/- 9.5 ml/m2 (all p less than 0.01). Heart rate fell significantly only after guanabenz. Plasma norepinephrine, unchanged after indoramin, fell in each patient after guanabenz; the mean value decreased from 746 +/- 332 to 461 +/- 255 pg/ml (p less than 0.01). Plasma renin activity increased only after indoramin. The data demonstrate: (a) a decrease in sympathetic activity due to blockade of alpha 1 adrenoreceptors produces marked peripheral and pulmonary vasodilation; (b) noradrenergic transmitter release in heart failure is regulated by alpha 2 receptors; (c) an alpha 2-mediated decrease in sympathetic activity and in plasma norepinephrine has a bradycardic effect but does not produce a vasodilator effect. Although the acute hemodynamic effects of indoramin were more prominent than those of guanabenz, the more favorable neurohumoral effects of guanabenz suggest the possibility of long-term benefit in the treatment of heart failure.

Acute Effects of Intravenous Indoramin on the Hemodynamic Adaptation at Rest and During Exercise in Chronic Congestive Heart Failure

Seven male patients (age 47-70 years) with congestive idiopathic (n = 4) or ischemic (n = 3) cardiomyopathy of functional class 2 (n = 5) or 3 (n = 2) were investigated. In the control study, cardiac output (Fick principle) and intravascular pressures were measured at rest in the supine position and during three consecutive bicycle exercise levels of increasing severity in the sitting position. One hour later, indoramin (0.09 to 0.17, mean: 0.12 mg/kg) was slowly injected over 10 to 20 min in the supine (n = 3) or sitting (n = 4) position and the same protocol was repeated 15 min later. After drug injection, one patient developed major postural hypotension and exercise data were not collected in this patient; data on six patients are thus presented. At rest, indoramin decreased mean heart rate from 91 to 77 beats/min, arterial blood pressure from 123/69 to 102/61 mm Hg, and mean pulmonary arterial pressure from 26 to 22 mm Hg. The effects of indoramin were similar during the three levels of exercise (analysis of variance). At the highest exercise level, heart rate was unchanged (from 135 to 138 beats/min) and cardiac output was slightly increased (from 8.6 to 9.6 L/min); blood pressure (from 166/87 to 155/78 mm Hg); pulmonary arterial pressure (from 49 to 42 mm Hg); mean capillary wedge pressure (from 31 to 22 mm Hg); systemic vascular resistances (from 1,065 to 863 dynes); and total pulmonary resistances (from 523 to 403 dynes) were all significantly lower after indoramin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Indoramin on Finger Circulation in Patients with Raynaud Disease

The effect of indoramin was investigated on finger circulation in 20 patients with primary Raynaud disease. After placebo run-in, indoramin (50 mg t.i.d. per os) and placebo were given double-blind and in randomized order, each for 6 (protocol 1) and 3 weeks (protocol 2). No significant changes in blood pressure and heart rate were observed. Finger blood flow, measured with venous occlusion plethysmograph, increased significantly (p less than 0.025) with indoramin as compared with placebo, and local calculated resistance decreased when measured at room temperature (protocol 1). In protocol 2 flow was measured at the end of a 6-min contact with water temperature of 40, 30, 20, 10 and 5 degrees C, respectively. It was shown that the difference between indoramin and placebo was largest at high temperatures and was clearly decreased at lower temperatures. Thus, the present data objectively document that indoramin is capable of favorably influencing skin circulation, but this effect is less pronounced at lower temperatures.

Effects of Indoramin and Metoprolol on Plasma Lipids and Lipoproteins

The effects of indoramin (n = 29) and metoprolol (n = 15) on lipid profiles in hypertensive patients were compared in a double-blind study. Blood samples were taken at baseline, weeks 3 and 4 of placebo administration, and after 4 and 8 weeks of active treatment. The following assays were performed: total cholesterol, total triglycerides, high density lipoprotein (HDL) cholesterol, HDL3 cholesterol, and apoproteins A, AI, and B. The following values were calculated: HDL2 cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol/HDL cholesterol ratio (Castelli risk ratio I), and LDL cholesterol/HDL cholesterol (Castelli risk ratio II). The results of an overall analysis showed the following significant changes (mean +/- SD) for indoramin: LDL cholesterol, from 129.50 +/- 38.29 to 114.00 +/- 32.41 mg/dl (p less than or equal to 0.001); apoprotein A, from 169.51 +/- 39.83 to 232.48 +/- 34.08 mg/dl (p less than or equal to 0.001); apoprotein AI, from 105.62 +/- 20.70 to 134.68 +/- 21.58 mg/dl; apoprotein B, from 110.13 +/- 34.88 to 122.34 +/- 32.13 mg/dl (p less than or equal to 0.05); and Castelli risk ratio II, from 2.38 to 1.96 (p less than or equal to 0.01). The following significant variations occurred for metoprolol: total cholesterol, from 201.54 +/- 49.21 to 191.80 +/- 51.88 mg/dl (p less than or equal to 0.05); apoprotein A, from 186.78 +/- 62.63 to 227.68 +/- 44.78 mg/dl (p less than or equal to 0.001); apoprotein AI, from 109.12 +/- 34.72 to 131.95 +/- 21.79 mg/dl (p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the Effect of Indoramin and Prazosin on Blood Pressure and Lipid Profiles in Essential Hypertension

The antihypertensive effect and the influence on lipid metabolism of the alpha-receptor blocking drugs indoramin and prazosin given in combination with hydrochlorothiazide were investigated in patients with mild to moderate essential hypertension. Following treatment with thiazide alone, indoramin or prazosin was added in a randomized double-blind fashion. Both indoramin and prazosin reduced blood pressure in relatively low doses in a similar magnitude and counteracted the unwanted effects of the diuretic on lipid metabolism. Side effects of indoramin and prazosin were generally mild and transient. The combination of diuretics with alpha-receptor blocking drugs appears to be a promising regimen for the treatment of essential hypertension because of its antihypertensive efficacy and because of its reduction of the unwanted side effects of the single drugs.

The Effect of Indoramin on Exercise Performance in Mild Hypertension

The alpha 1-adrenoceptor antagonist indoramin is proposed to reduce arterial blood pressure without a concomitantly significant increase in heart rate (HR). The present study involves assessment of the effect of alpha 1-adrenoceptor antagonism in patients with mild hypertension on the HR/oxygen consumption (Vo2) relationship, which has previously been shown to indicate improvement in cardiorespiratory fitness following exercise training. A total of 16 patients with a systolic blood pressure of 140-200 mm Hg and diastolic blood pressure of 95-110 mm Hg were examined. A double-blind, placebo-controlled study design was utilized. Following initial observations, the patients were randomized into one group (a) of seven patients who were given a placebo, indoramin, and finally placebo, and a second group (b) of nine patients who were given the two agents in the reverse order, i.e., indoramin, placebo, indoramin; each intervention lasted for 2 weeks and indoramin was given in a dose of 75 mg/day. Indoramin caused a reduction in the elevation of the computed regression line relating HR to Vo2 (a shift to the right), such that at the same HR a greater Vo2 was attained in 11 of the 16 patients in comparison with the baseline exercise test. Pooled results showed a shift of the HR/Vo2 regression line to the right when indoramin was compared with baseline (p less than 0.05) or placebo. In the same patients, indoramin caused a decrease in arterial blood pressure during exercise relative to baseline or placebo periods, and a decrease in the HR during exercise relative to baseline period, but not when compared with placebo periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Antianginal and Haemodynamic Effects of α1-Adrenoceptor Blockade

We studied the effects of alpha 1-adrenoceptor blockade with indoramin on exercise tolerance in 15 patients with chronic stable angina using a double-blind crossover protocol. Thirteen patients had been receiving beta-adrenoceptor blocking drugs and nitrates. The therapy of these patients was continued unchanged throughout the study. Indoramin, in a dose of 25 mg three times daily, prolonged exercise duration by 17% (p less than 0.01) and increased oxygen consumption during exercise by 21% (p less than 0.01), while the maximal double product was unchanged. This increase in exercise capacity was associated with significant attenuation in ST segment depression during exercise. To investigate the mechanism of this antianginal effect, we studied the effects of indoramin (0.2 mg/kg i.v.) on coronary and systemic haemodynamics in a further 11 male patients with chronic stable angina who were receiving beta-adrenoceptor blocking drugs. Measurements were obtained during sinus rhythm and during atrial pacing from 100 beats/min, incremented by 20 beats/min at intervals of 3 min until the onset of angina. Indoramin had no effect on resting heart rate (64 +/- 2 vs. 67 +/- 2 beats/min), but did prolong pacing time to angina (7.4 +/- 0.7 vs. 5.4 +/- 0.5 min; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental Evidence for the Antiarrhythmic Action of Indoramin

The effects of indoramin on cardiac conduction and its antifibrillatory action were investigated and compared with those of mexiletine (class I antiarrhythmic agent), sotalol, and prazosin. In isolated guinea pig atria, indoramin 1 microgram/ml reduced spontaneous rate by 31 +/- 1.0% (mean +/- SE, n = 6) and maximal driving frequency by 25 +/- 1.2% (n = 4). Mexiletine 3 micrograms/ml reduced maximal driving frequency by 35 +/- 1.4% (n = 4) but reduced spontaneous rate by only 13 +/- 2.0% (n = 4). In isolated, perfused, electrically driven (2.5 Hz) guinea pig hearts, indoramin 1 microgram/ml increased the ST interval by 22 +/- 1.9% (n = 6) with no effect on the QRS interval. Higher concentrations (3 micrograms/ml) also increased the QRS interval by 21 +/- 4.0%. In anaesthetized cats, indoramin 6 mg/kg i.v. (infused over 30 min) reduced systolic blood pressure by 36 +/- 3.6% (n = 6) and heart rate by 35 +/- 2.2%, and increased the ST interval by 31 +/- 5.3% and the effective refractory period by 45 +/- 3.2% but had little or no effect on the QRS interval (12 +/- 2.9%) and diastolic electrical stimulation threshold (7 +/- 6.8%). Indoramin 10 mg/kg increased the QRS interval and diastolic electrical stimulation threshold by 20 +/- 2.8 and 23 +/- 2.5%, respectively. Analogous experiments with mexiletine 15 mg/kg showed little changes in cycle length (7 +/- 1.3%), effective refractory period (21 +/- 2.8%), and the ST interval (6 +/- 2.5%); however, there was a marked increase in diastolic threshold (91 +/- 8.9%). Sotalol 15 mg/kg had a cardiac profile similar to that of indoramin.(ABSTRACT TRUNCATED AT 250 WORDS)

A Double-Blind Comparison of Indoramin and Pindolol Added to Hydrochlorothiazide for the Treatment of Mild to Moderate Hypertension

Sixty patients with mild to moderate essential hypertension, uncontrolled with diuretics alone, were evaluated in a double-blind randomized study that compared the effect of indoramin plus hydrochlorothiazide with that of pindolol plus hydrochlorothiazide. Following a 2-week period during which the patients were treated with 50 mg/day of hydrochlorothiazide, the patients were treated either with indoramin, 50-100 mg/day (n = 29), or with pindolol 10-20 mg/day (n = 30), in addition to the diuretic for 12 weeks. Systolic and diastolic blood pressures were significantly reduced after 2 weeks of treatment with indoramin or pindolol; blood pressure reduction was maintained for the 12 weeks of treatment. There were no significant differences between the indoramin and pindolol groups with respect to the changes in blood pressure. Blood pressure was controlled (less than or equal to 90 mm Hg) in 70% of the indoramin-treated patients and in 80% of the pindolol-treated patients. The difference was not significant. Heart rate was reduced after pindolol but not after indoramin. Side effects occurred in 20 patients (67%) treated with indoramin and in 14 patients (47%) treated with pindolol; the difference between the groups was not significant. Eight patients in the indoramin group and 10 patients in the pindolol group withdrew before completion of the study. In the indoramin group, four patients withdrew because of side effects and four because of lack of efficacy. In the pindolol group, five patients withdrew because of side effects and three because of lack of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Effects of Indoramin and Prazosin in Combination with Hydrochlorothiazide

The safety and efficacy of indoramin and prazosin added to hydrochlorothiazide (HCTZ) were compared in a double-blind trial involving 209 patients with mild to moderately severe essential hypertension. Patients whose supine diastolic blood pressure (SDBP) did not decrease to less than or equal to 90 mm Hg after 6 weeks of HCTZ therapy had indoramin or prazosin added to their regimen. Mean SDBP during 6 months of combination therapy with either regimen decreased by approximately 10 mm Hg from that at the final evaluation during HCTZ therapy (p less than 0.001); differences between the groups were not statistically significant. Mean heart rate was unchanged, whereas mean weight increased (p less than 0.001) above final HCTZ values by approximately 2 kg in both groups. Mean weight increased significantly (p less than 0.01) from baseline values, however, only in the prazosin/HCTZ group. Approximately 95% of the patients in each group had clinically significant decreases in SDBP. Fatigue or tiredness and dizziness were the most commonly reported adverse effects, and their frequencies were not significantly different in the two groups. Cardiac arrhythmias occurred only in patients in the prazosin/HCTZ group and were significantly (p less than 0.05) more frequent than among patients in the indoramin/HCTZ group; less severe adverse experiences, i.e., dry mouth, ejaculatory problems, drowsiness, and sedation, were significantly (p less than 0.05) more frequent in the indoramin/HCTZ group. When added to HCTZ, indoramin and prazosin are equally safe and effective in the treatment of hypertension.

Indoramin in the Hypertensive Diabetic Patient

In 32 hypertensive diabetic patients a study was performed to determine the effects of indoramin on blood pressure and blood glucose, plasma insulin, C-peptide, serum total cholesterol, and triglyceride levels. All patients evaluated showed a significant fall in blood pressure with daily doses of 50 to 200 mg of indoramin. In six insulin-dependent diabetic patients there was no change in diabetic control and no effect on the incidence of hypoglycaemia. In 18 noninsulin-dependent diabetics monitored for 3 months and in 14 followed for 12 months, there was no significant change in glucose tolerance after a 75 g glucose dose; mean plasma C-peptide levels and 2 h insulin levels were increased at 12 months. Mean weight and mean fasting cholesterol and triglyceride concentrations were unchanged. Nine patients withdrew because of side effects, mainly drowsiness and lethargy.

Improvement in angina pectoris with alpha adrenoceptor blockade.

The effects of indoramin, a selective alpha 1 adrenoceptor antagonist, on exercise tolerance were studied in 15 patients using a random double blind crossover protocol. All patients had chronic stable angina, for which 13 had been receiving beta adrenoceptor blocking drugs and nitrates, and these were continued unchanged throughout the study. An initial open challenge with indoramin in eight patients with chronic stable angina showed no serious adverse effects. In a dose of 25 mg three times daily indoramin prolonged exercise duration and increased oxygen consumption during exercise, while the maximal double product was unchanged. The increased exercise capacity was associated with a reduction in ST segment depression during exercise. Side effects included failure of ejaculation in one patient and tiredness in five. These results indicate than alpha 1 adrenoceptor blockade may provide useful additional benefit to patients with stable angina pectoris who are already receiving beta blockers and nitrates.

The effect of indoramin on plasma lipids in hypercholesterolemic patas monkeys

In patas monkeys fed a high cholesterol diet, chronic dosing with the antihypertensive agent indoramin increases the cholesterol ratio by raising the plasma HDL-C concentration. Epidemiological evidence suggests that increasing HDL-C reduces the incidence of coronary heart disease (CHD). If, therefore, indoramin is able to evoke these changes in man it may be expected to favourably influence the progress of CHD.

Indoramin‐prolongation of repolarization time, a mechanism of bradycardia in man?

The effect of indoramin, a selective alpha 1-adrenoceptor antagonist, on ECG time intervals in normal man was studied. Significant prolongation of QTc was observed after indoramin 100 mg, with no change in QRS duration. In addition, the slope of the RR/QT relationship was changed by indoramin 100 mg. These results suggest that indoramin may have Class III antiarrhythmic activity. If such activity were to affect the SA node, it may explain at least in part the observed lack of reflex tachycardia after indoramin administration.

Antiarrhythmic and Electrophysiological Effects of Indoramin during Myocardial Ischaemia and Reperfusion

Antiarrhythmic and Electrophysiological Effects of Indoramin during Myocardial Ischaemia and Reperfusion

Effect of indoramin on human sperm motility.

Effect of indoramin on human sperm motility.

Effect of indoramin and propranolol on cardiovascular response to cold in hypertensive patients.

Immersion of the hand into ice water (cold-pressor test) in nine hypertensive subjects induced elevation of mean blood pressure, increase of vascular resistance in the extremities, decrease of blood flow in the extremities, and increase in heart rate. The preejection phase of systole was not altered. Indoramin and propranolol, each alone and together, attenuated the pressor and other cardiovascular responses. Submaximal exercise increased heart rate during placebo treatment, a response only partially attenuated by indoramin, propranolol, and their combination, but it did not induce changes in mean blood pressure during any of the treatments.