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At least 19 recordsLinked to original sources

PubMedDate not supplied

The influence of dihydroergotamine on adenosine-induced and reactive coronary vasodilation. Interaction of dihydroergotamine and coronary vasodilation.

The influence of dihydroergotamine on adenosine-induced and reactive vasodilation after long and short periods of coronary artery occlusion was investigated in thoracotomized dogs. Adenosine-induced vasodilation (intracoronary administration) and vasodilation after long periods of coronary artery occlusion (25-35 beats) were similarly influenced, i.e. decreased by the i.v. administration of 10 mug/kg dihydroergotamine. By contrast vasodilation after short periods of coronary artery occlusion (4-7 beats) tended to be increased. This difference in response is thought to arise from two distinct mechanisms of coronary vasodilation after coronary artery occlusion depending on the duration of the occlusion period. The vasodilation after short periods of coronary artery occlusion possibly corresponds to physiological autoregulation. With longer periods of coronary artery occlusion an additional, consecutive mechanism is called into action.

Adenosine↗

PubMed1977

[Quantitative assessment of drug-induced prophylaxis of postoperative thromboembolism. Comparison of frequencies of deep vein thrombosis and pulmonary embolism using acetylsalicylic-acid, dextran, dihydroergotamine, low-dose heparin and the fixed combination of heparin and dihydroergotamine (author's transl)].

2136 patients in general surgery, gynaecology and urology were investigated by the 125I-fibrinogen-uptake-test for detection of postoperative deep vein thrombosis (DVT). They received at random one of low-dose heparin, dihydroergotamine, the fixed combination of both drugs (Heparin-Dihydergot), low molecular weight dextran and acetylsalicylic-acid (ASS). When DVT was detected repeated lung perfusion scintigraphies were carried out for diagnosis of embolic pulmonary perfusion defects. Results demonstrate the outstanding effect of Heparin-Dihydergot, which is not only 2-3 times better than the anti-thrombotic standard low-dose heparin but also eliminates almost completely the risk of postoperative embolism. The preventive efficacy of ASS and dextran must be considered to be poor and not comparable to that obtained when using heparin, dihydroergotamine or the combination. Now Heparin-Dihydergot is the new standard with which all prophylactic procedures should be compared.

Adult↗

PubMed1977

Effects of dihydroergotamine methanesulfonate on the microcirculation of the rat cremaster muscle.

Effects of dihydroergotamine on the microcirculation of the rat cremaster muscle were investigated microscopically using colour photographic technique. 1. Dihydroergotamine 10(-4) g/ml constricted arterioles of the rat cremaster. 2. Dihydroergotamine 10(-4) g/ml produced a significant contraction of venules. 3. Dihydroergotamine 10(-4) g/ml markedly inhibited the contractile response of noradrenaline 10(-6) g/ml on arterioles of the rat cremaster. The results suggest that dihydroergotamine has an appreciable vasoconstrictive action, especially upon venules, and that dihydroergotamine also has an adrenergic alpha-receptor blocking action. By means of highly sensitive negative colour film we obtained a satisfactory photograph of the rat cremaster's circulation.

Animals↗

PubMed1978

Dihydroergotamine: pharmacokinetics and usefulness in spinal anaesthesia.

In a double-blind study, 0.5 mg of dihydroergotamine or the same volume of placebo was used to prevent hypotension caused by spinal anaesthesia. The plasma concentrations of dihydroergotamine were determined by a new radioimmunoassay developed for ergot alkaloids, and pharmacokinetic calculations were based on the equation of a two-compartment open model. No significant changes were observed in the heart rates of the two patient groups. In Group I, which received dihydroergotamine, significant increased in both systolic and diastolic blood pressures were measured after drug administration, and, compared to the base-line measurements before spinal anaesthesia, no significant decreases in systolic or diastolic blood pressures were recorded. In contrast to Group I, there was a significant decrease in both systolic and diastolic blood pressures in the placebo Group II during spinal anaesthesia. There were no significant differences, however, in the temperature of the great toe between Groups I and II. Dihydroergotamine disappeared quickly from plasma, with a mean alpha-phase half-life of 1.35 min, which explained its rapid effect on blood pressure. Beta-phase half-life (mean 23.20 min), the volume of distribution at beta-phase (mean 0.25 I/kg), and the total plasma clearance (mean 1562.8 ml/min) indicate rapid elimination of the drug from the body.

Aged↗

PubMed1978

The pharmacokinetics of dihydroergotamine in the beagle.

After single 0.5-mg nad 1.0-mg i.v. injections, dihydroergotamine, as measured by a radioimmunoassay, disappeared quickly from the plasma of beagles, with a mean alpha-phase half-life of 1.32--1.91 min. This explains its effect of rapidly lowering the temperature of the ear of the dog. Its short beta-phase half-life (mean, 40.79--70.13 min), a moderately low volume of ditribution at beta-phase (mean 1.50--3.46 L/kg) and a rather high plasma clearance value (mean, 311.67--587.88 ml/min) indicate a rapid elimination of the drug from the organism. The 24-hr urinary excretion of dihydroergotamine was 2.7% of the 0.5-mg i.v. dose and 2.3% to 3.1% of the 1.0-mg i.v. dose. A measure of the amount of a 7.5-mg p.o. dose of the drug reaching the systemic circulation was obtained from the ratio of the area under the plasma curve after p.o. administration to that after i.v. administration, corrected for the different amounts given by the two routes. Only 1.2--1.4% of the 7.5-mg p.o. dose of dihydroergotamine reached the systemic circulation. There were no significant differences in the plasma levels of dihydroergotamine after a single dose of the two preparations tested, Vasogin (Leiras) and Orstanorm (Sandoz), given either by the oral or intravenous route.

Animals↗

PubMed1978

[Influence of dihydroergotamine and leg compression on the blood volume in different regions of the body (author's transl)].

After intravenous injection of 99mTc labelled autologous erythrocytes the radioactivity of a definite body-region is proportional to the local blood volume. By whole body scintigraphy it is possible to assess simultaneous changes of blood volume in different interesting regions. By this method the influence of 1 mg dihydroergotamine i.v. was investigated in 10 patients and of compression of both legs by inflatable leg cuffs (Jobst) with pressures of 25 and 40 mmHg (3,3 and 5,3 kPa) in 7 patients. After dihydroergotamine statistically significant decreases of blood volume were found in the legs and arms and increases in the thorax and liver. Over the abdominal region there was a statistically not significant decrease of blood volume. After leg compression a statistically significant decrease of blood volume in the legs and an increase in thorax, liver and abdomen were found. The arms showed a statistically not significant blood volume increase. The blood volume diminishing effect of dihydroergotamine in the legs was 20,4% in average, of a leg compression (25 mmHg=3,3 kPa) 33,4%. Contrary to the general opinion a reduction of blood volume was also found in legs with severe varicosis. The diminution of blood volume is even more intense in such cases than in normal legs. The results after dihydroergotamine are explained by its well known constrictor effect on the capacitance vessels in the extremities.

Abdomen↗

PubMed1979

Prophylaxis for postoperative deep-vein thrombosis. Synergistic effect of heparin and dihydroergotamine.

Randomized clinical trials in 300 patients undergoing major abdominal surgery or hip replacement arthroplasty were performed to investigate the efficacy of dihydroergotamine mesylate, heparin calcium, or a combination of dihydroergotamine with heparin in preventing postoperative deep-vein thrombosis (DVT). The diagnosis of DVT was established by an uptake test using fibrinogen labeled with iodine 125; in patients undergoing hip replacement, phlebography was also employed to confirm or refute the presence of isotopic thrombi. The data indicate that the combination of dihydroergotamine and heparin is more effective than heparin or dihydroergotamine alone in preventing DVT.

Abdomen↗

PubMed1979

[Effect of dihydroergotamine on pulmonary perfusion in acceleration stress (author's transl)].

An orthostatic circulatory load of varying degree (1-4 G) can be simulated by means of a human centrifuge. This results in a partial shifting of the intrathoracic blood volume into the capacity vessels of the lower extremity. In the pulmonary region, this is associated with a decrease in perfusion from the apical to the basal segments, which can be demonstrated by double nuclide perfusion scintigraphy. The degree of change in pulmonary perfusion was determined quantitatively in 26 volunteers by perfusion scintigraphy before and during acceleration, and the influence of dihydroergotamine (Dihydergot) was studied. The results show that the redistribution of the polmonary blood volume into the lower parts of the body can be largely prevented by Dihydergot. Pulmonary perfusion remains almost unchanged, compared with the initial value, up to an acceleration stress of 3 G, following intravenous injection of 0.5 mg dihydroergotamine. After oral administration (6 mg/d over 12 days), this applies to 1 and 2 G. Hence, dihydroergotamine represents, so to say, a "pharmacological anti-G suit".

Acceleration↗

PubMed1978

[The effect of etilefrine and dihydroergotamine on sympathetic nervous system activity when standing up (author's transl)].

Systolic blood pressure, heart rate and concentrations of adrenaline, noradrenaline and dopamine as well as plasma dopamine-beta-hydroxylase (DBH) were measured in 22 subjects in recumbency and on standing up. Six subjects each had previously been given intravenously dihydroergotamine (0.5 mg) or etilefrine (0.25 mg/min) or a placebo. It was demonstrated that orthostasis leads to an increased activity of the sympathetic nervous system and the adrenal system. After administration of dihydroergotamine there was a diminished reaction of the sympathetic nervous system with an increase of venous tone which counteracted the decrease in cardiac output. Etilefrine, on the other hand, inhibited the sympatho-adrenal reaction on orthostasis and decreased the liberation of adrenaline. It acts directly via stimulation of alpha-and beta-receptors and is thus predominantly indicated if there is insufficient response of the baroreceptor reflex at its efferent limb.

Adult↗

PubMedDate not supplied

Antidiarrheal effects of dihydroergotamine.

Dihydroergotamine (DHE), an alpha-adrenergic blocking agent, rapidly improved 121 out of 123 diarrheal patients. A hypotonic sigmoid and a hyperreactive rectum were found in these patients. Manometric studies of the distal colon showed that DHE counteracts the rectal hyperactivity and increases sigmoidal tone. On the other hand, anticholinergic drugs and/or emotional stimuli accentuate the rectal hyperactivity of diarrheal patients. Both features could be due to an unbalanced neurologic control of the gastrointestinal tract with dominance of the alpha-adrenergic over the cholinergic activity. Diphenoxylate (DPO) suppressed the diarrhea in two patients not improved by DHE. Furthermore, DPO reinforced the therapeutic success of DHE in 11 lactose intolerance diarrheal patients, suggesting that the two drugs exert their effects by means of different mechanisms.

Adolescent↗

PubMed1977

Catecholamine-sensitive adenylate cyclase of human fat cell ghosts. Inhibition of isoproterenol-stimulation by dihydroergotamine.

Isoproterenol-activation of the adenylate cyclase system of human fat cell ghosts was markedly inhibited by dihydroergotamine which had no effect on basal and NaF-stimulated enzyme activity. Our results indicate that the antilipolytic action of this substance in human adipose tissue is probably due to inhibition of catecholamine-sensitive adenylate cyclase activity.

Adenylyl Cyclases↗

PubMed1979

Dihydroergotamine therapy in symptomatic postural hypotension.

The clinical response to therapy with dihydroergotamine (DHE) has been evaluated in one patient with idiopathic orthostatic hypotension. The results of tests performed on the autonomic nervous system are recorded, and the evidence for a central defect in postural blood pressure control is presented. Tilt table testing over a two-month period confirmed the beneficial effect of the medication in preventing profound falls of blood pressure. The dose required (20 mg/day) was higher than previously reported.

Aged↗

PubMed1978

Differences in dihydroergotamine antagonism of glucose release by catecholamines, glucagon and adenosine 3',5'-monophosphate in rabbit liver slices.

1 Quantitative studies were made on the glucose release from rabbit liver slices in vitro induced by a range of concentrations of (-)-adrenaline (Ad), (-)-isoprenaline (Iso), glucagon and adenosine 3',5'-monophosphate (cyclic AMP) in the presence and absence of several concentrations of dihydroergotamine (DHE). 2 DHE (3.16 X 10(-6) M) shifted the Ad log concentration-response (LCR) curve to the right and also reduced the maximum response; at a higher concentration (3.16 x 10(-5) M) it produced a greater shift to the right of the LCR curve and caused a reduction in the slope and a larger depression of the maximal responses. The LCR curve to Iso was similarly affected by this higher concentration of DHE. 3 DHE (1 X 10(-5) M) produced no significant effect on the LCR curves of glucagon or cyclic AMP and even at 1 x 10(-4) M DHE caused only a slight depression of the maximal responses to both agonists without any modification of the lower major portions of the curves. 4 These data indicate a selective antagonism by DHE at the rabbit liver adrenoceptor and, since the maximal responses to catecholamines were depressed by a lower concentration of DHE than was required to produce a slight depression of the responses to glucagon and cyclic AMP, the antagonism of DHE against catecholamines does not appear to be at a site beyond the formation of cyclic AMP, but rather at a site more intimately related to the adrenoceptor.

Animals↗

PubMed1976

Circulatory effects of dihydroergotamine in patients with disturbed sympathetic vasomotor control with special reference to postural hypotension.

In five patients with postural hypotension (disturbed sympathetic vasomotor control) the effect of intravenous and oral administration of dihydroergotamin (DHE) has been studied. The therapeutic effect of oral administration of DHE has also been compared to the effect of treatment with an antigravity suit. Following intravenous administration of DHE, systemic and central venous pressure increased in all cases. The effect on cardiac output was negligible and consequently the calculated total peripheral vascular resistance increased. Orthostatic tolerance increased in all cases. During long-term oral administration the effect was comparable to that obtained with an antigravity suit. The increased orthostatic tolerance is explained by a constrictive effect on both capacitance and resistance vessels. In order to analyze the influence of a functional denervation on the effect of DHE on peripheral circulation, a study has also been performed during epidural anaesthesia of the lower body in 11 patients. In the legs which were deprived of sympathetic tone intravenous administration of DHE caused constriction of resistance vessels. In the intact forearm there was a decrease of tone in the resistance vessels. The results indicate that DHE - apart from its well-known venoconstrictive effect - also may constrict resistance vessels when they are subjected to a low sympathetic nervous outflow.

Administration, Oral↗

PubMed1978

[Comparative studies on the protective effect of etilefrin and dihydroergotamine in circulatory instability after blood donation].

In 20 female and 40 male subjects with circulatory instability, the response of pulse rate and blood pressure to blood loss and orthostasis was studied under the condition of protective pretreatment with drugs known to improve venous return by increasing the tone of capacitance vessels. Before blood loss (420 ml), in a cross-over double-blind procedure, each subject obtained 10 mg etilefrin or 2 mg dihydroergotamine, both administered orally. The procedure was repeated after at least 8 weeks. At this time, the subject obtained the drug which was not given in the first examination. By comparison of pulse rate and blood pressure taken after pretreatment, the statistical evaluation did not reveal any differences in the effectiveness of one or the other drug on the response to hypovolemic and orthostatic conditions. Patients preferred etilefrin.

Adolescent↗

PubMed1977

[Blood volume displacement under oral dihydroergotamine during orthostatic strain (author's transl)].

During the course of a double-blind study in 30 orthostatically unstable adolescent subjects, the effect of oral dihydroergotamine (DHE) on the orthostatic circulatory regulation was examined. During standardized orthostatic strain the volume of blood sinking into the two legs is statistically significantly reduced to 125 +/- 61 ml (29%) under the influence of DHE after standing for only 11 sec. Furthermore, there is a significant reduction of the maximal arterial influx into the lower extremities as well as the resting heart rate and the maximal heart rate during orthostatic strain. No significant changes could be detected in the placebo group. Consequently, DHE is suitalbe for the treatment of the these disturbances of orthostatic circulatory regulation due to increased elasticity of the capacitive vessels in the lower extremities.

Administration, Oral↗

PubMedDate not supplied

[Effect of dihydroergotamine, reserpine and anapriline on the pharmacokinetics and metabolism of norsulfazole in rats].

In in vivo experiments with rats anapriline (1 mg/kg) greatly reduced the level of gastrically introduced norsulfazol (200 mg/kg) in the blood, liver, kidneys, stomach, small and large intestine both in healthy rats as well as in those with experimental gastritis provoked by acetylsalicylic acid twice introduced into the stomach. Under the influence of anapriline the acetylization of norsulfazol in the liver would become 4.7 times less intensive. Dihydroergotamin (10 mg/kg) did not influence the absorption, distribution and acetylization of norsulfazol. Reserpine (10 mg/kg) brought down the amount of free norsulfazol in the gastro-intestinal tract and reduced the quantity of acetylized norsulfazol in the blood, stomach, small and large intestines. The acetylization changes in the kidneys were not significant. In the springtime the intensity of the norsulfazol acetylization increases by more than twice. The described results bear witness to the participation of beta-adrenoreceptors in the transport and metabolism of norsulfazol.

Absorption↗

PubMed1978

Intramuscular absorption of dihydroergotamine in man.

In order to prevent hypotension, 1.0 mg of dihydroergotamine (Vasogin) was injected intramuscularly to 10 patients 5 minutes before spinal anaesthesia. The peak plasma concentrations were measured by a radioimmunoassay as early as at 30 minutes after drug administration, indicating a fast intramuscular absorption. According to the plasma levels the drug has to be given 15-30 minutes before spinal anaesthia.

Absorption↗