Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1432-1041
    Keywords: Benserazide ; decarboxylase inhibition ; alpha-methyldopa ; essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-blind study, the dopa-decarboxylase inhibitor benserazide (375 mg/day for 3 days and 750 mg/day for further 3 days) and a placebo were given orally in combination with individually effective doses of alpha-methyldopa (mean 1.5 g/day) to 3 hospitalized patients with essential hypertension. Alpha-methyldopa (α-MD) alone lowered blood pressure from 165/107 to 136/93 mm Hg (P〈0.05). Benserazide did not alter the hypotensive effect of α-MD, although the decarboxylation of α-MD was markedly reduced, as shown by the urinary excretion of alpha-methyldopamine (α-MDA). During administration of α-MD alone, the ratio α-MD/α-MDA in urine of the 3 patients was 8:1, 7:1 and 22:1, respectively. When benserazide 375 mg/day was added the ratio rose to 31:1, 31:1 and 35:1; the ratio was 37:1, 18:1 and 46:1 at the higher dose of inhibitor. In a double-blind crossover study the effect on blood pressure of 3 weeks of treatment with α-MD (mean 1.75 mg/day), benserazide (375 mg/day), placebo and their combinations were compared in 5 hypertensive subjects. Again, benserazide did not influence the antihypertensive action of α-MD. To study whether benserazide entered the CNS, a single oral dose of14C-benserazide of 125 mg was given to 2 patients who were to undergo diagnostic lumbar puncture. Two hours after intake of the labelled drug, when radioactivity in blood had reached a maximum, the concentration of radioactivity in spinal fluid was less than 1% of the plasma level. Thus, the antihypertensive action of α-MD was not influenced by oral doses of the decarboxylase inhibitor benserazide. The results suggest that benserazide in doses up to 750 mg/day does not affect central decarboxylation of α-MD and that this antihypertensive agent lowers blood pressure by a central action.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-1041
    Keywords: Monoamine oxidase ; irreversible enzyme inhibition ; benmoxine ; duration of inhibition in man ; methods for MAO determination in man ; multiplicity of deaminating enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Investigations with an irreversible monoamine oxidase (MAO) inhibitor were performed in man in order to correlate biochemical, pharmacological, and clinical changes during and after MAO inhibition. — Six healthy volunteers were treated with the hydrazine MAO inhibitor benmoxine (1-α-methylbenzyl-2-benzoyl hydrazine) in a dosage of either 75 mg/day for 4 weeks, or with 75 mg/day for 2 weeks, and 100 mg and 125 mg per day during the 3rd and 4th week respectively. — 1. Inhibition of plasma MAO occurred rapidly and was almost complete after one week of treatment with 75 mg/day benmoxine. After discontinuation of the treatment, there was rapid normalization of enzyme activity (within one week) and a subsequent rebound. — 2. Inhibition of blood platelet MAO was also rapid and almost total, but the return to normal did not occur earlier than 3 weeks after cessation of the drug. — 3. The serotonin content of blood platelets increased cumulatively and dose-dependently during the treatment period. Normal serotonin levels were found 2–3 weeks after treatment was discontinued. — 4. Urinary tryptamine excretion was not increased when the lower benmoxine dose was given. An immediate threefold rise was observed with the higher dosage. This effect disappeared after about one week. — 5. Due to progressive MAO inhibition, the blood pressure rising effect of intravenously infused tyramine also increased cumulatively. This effect was dose-dependent: three- and fivefold potentiation were found after 4 weeks of treatment with the two different dosage schedules. — The mydriatic response to tyramine instilled into the conjunctival sac was also enhanced after 4 weeks of treatment. 6. Cardiovascular dysregulation could be detected (Schellong test, after exercise) only when the higher doses of inhibitor were given, i.e., after 4 weeks, when the pressure response to tyramine was increased to about 5 fold. — It is concluded that only the combined application of several methods (biochemical, pharmacological and clinical investigation procedures) permit definite conclusions to be drawn about the time course and extent of MAO inhibition in man.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; human plasma ; sympathetic activity ; physical stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma dopamine-β-hydroxylase activity after an almost maximum work load (bicycle ergometer; 100–250 watt for 6–10 min) has been investigated in 34 healthy volunteers. In all the experiments the enzyme activity increased by about 25%. The percentage increase in the enzyme activity was independent of the initial enzyme level, which showed extreme inter-individual variation (range 4 to 340 enzyme units). After a resting period of one hour the raised enzyme activity had returned to normal. It appears that a high resting level of the enzyme may be due to its rapid turnover, i.e. rapid release from the sympathetic nervous system and its speedy elimination from the plasma, and, low basal activity may be indicative of slow turnover. — The increase in the activity of dopamine-β-hydroxylase in plasma during exercise is a measure of the acute elevation of sympathetic tone.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; man ; plasma ; sympathetic activity ; halothane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As an index of sympathetic nervous system activity, the level of dopamine-β-hydroxylase (DBH) in plasma was measured in 82 children, mean age 6±0.3 years, before and during halothane anaesthesia. Plasma DBH fell markedly in 50% of cases irrespective of the anaesthetic technique, i.e. halothane with or without nitrous oxide, and with or without premedication by pethidine and/or atropine; enzyme activity was unchanged in 25% of the children; and in the remaining 25%, DBH activity increased. The heart rate fell significantly in cases in whom DBH activity was lowered, and it remained almost unchanged, when DBH rose during anaesthesia. A fall in plasma DBH activity during anaesthesia was found particularly in children who appeared excited and anxious before anaesthesia; enhanced preanaesthetic sympathetic tone in this group was indicated by plasma DBH activities and heart rates higher than in the other groups. It is concluded that halothane may not only reduce elevated sympathetic activity, but also in most cases may oppose sympathetic counter-regulation which should occur in reponse to its direct cardiovascular depressant effect.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the function of dopamine-β-hydroxylase (DBH) in human plasma, dopamine, its natural substrate, was infused intravenously in 22 healthy volunteers. Their plasma DBH activities showed great interindividual variations (31–301 units/ml). The infusion rates of dopamine required to increase systolic blood pressure (BP) by 30 mm Hg differed considerably between the subjects, and ranged from 3,0 to 11,6 µg/kg/min. No correlation could be shown between the various dopamine doses and individual plasma levels of DBH. It was concluded, therefore, that plasma DBH in the blood stream was enzymatically inactive. Experiments with human plasma DBH in vitro also support this interpretation. Consequently, interindividual differences in the effects on BP during dopamine infusion cannot be due to pressor effects of noradrenaline synthesized by plasma DBH.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-1041
    Keywords: Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy untrained volunteers the increase in plasma dopamine-β-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130±3% and 820±71%, respectively; the adrenaline concentration in plasma increased only to 150±19% (p〉0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net “overflow” from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20 – 22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-1041
    Keywords: Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75–100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2–4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30–150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the directβ-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-1041
    Keywords: propranolol ; noradrenaline ; normotension ; withdrawal ; exercise ; effect duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of acute and chronic treatment with the adrenergic beta-receptor blocking agent propranolol (P) on blood pressure (BP), heart rate (HR) and plasma catecholamine concentration (CA) was studied in 7 normotensive healthy volunteers, and in 5 normotensive patients with cardiac neurosis, at rest, during physical exercise and after sudden withdrawal of the drug. The first oral dose of P 120 mg as well as chronic treatment (3×80 mg/day for 3 months) caused a significant reduction in HR and supine BP. Resting values of CA were not changed. After sudden withdrawal of the long-term therapy with P, supine BP and HR returned to normal, and again, resting levels of CA remained unchanged. A physical exercise test, performed 2 1/2 days after withdrawal of the betablocker, was not indicative of a transient sympathetic hyper-response. Striking effects of the drug on CA were observed during acute and chronic treatment with P when physical exercise was performed (bicycle ergometer, 150 W). Exercise values of CA were about twice as high during P treatment as without the drug, when the exercise test was performed 2 h after the first oral dose. At the same time, however, exercise BP and HR were significantly reduced. Similar reactions during the exercise test were also seen during chronic treatment with P, when the test was performed 2 hours after the last dose of the drug. But, when the exercise test was undertaken during chronic treatment 8 h after drug intake, the drug effect on CA had disappeared, whereas the effects on BP and HR still were present. The dissociation during chronic treatment between the effect on the duration of plasma CA and that of the pharmacodynamic responses to beta-adrenergic blockade with P is the principal finding of the study. A hypothesis is offered for interpretation of the observations. The time interval between measurement of drug effect and drug intake must be carefully observed in assessing different or controversial drug responses.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-1440
    Keywords: Adrenaline ; Noradrenaline ; Adrenal medulla ; Pheochromocytoma ; Hypertension ; Adrenalin ; Noradrenalin ; Nebennierenmark ; Phäochromozytom ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 10 Personen (5 mit normalem Blutdruck, 4 mit essentieller Hypertonie, 1 mit renaler Hypertonie) wurden die lokalen Katecholaminkon-zentrationen im Blut der Vena suprarenalis, Vena renalis, Vena cava inferior und Vena iliaca mit einer radioenzymatischen Methode bestimmt. Es fanden sich folgende Konzentrationen pro Milliliter Plasma: (1) In der Vena suprarenalis der linken Nebenniere 13,87±8,18 ng Adrenalin und 2,82±1,82 ng Noradrenalin; (2) in der Vena renalis, nach der Mischung mit dem Blut der einströmenden Vena suprarenalis, 1,44±1,13 ng Adrenalin und 0,37±0,18 ng Noradrenalin; (3) in der Vena cava inferior, cranial der Nierenvenenzuflüsse, 0,16±0,10 ng Adrenalin und 0,30±0,10 ng Noradrenalin; (4) in der Kreislaufperipherie, zum Beispiel im Blut der Vena iliaca, betrug die Adrenalinkonzentration mit 0,09±0,03 ng nur noch 1/154 der ursprünglichen Konzentration im Nebennierenvenenblut, die Noradrenalinkonzentration lag hier bei 0,24±0,14 ng/ml Plasma. Unter der Annahme, daß das vom Nebennierenmark freigesetzte Noradrenalin den gleichen Verteilungs- und Eliminationsmechanismen wie Adrenalin unterliegt, wurde errechnet, daß unter basalen Sekretionsbedingungen im Durchschnitt nur 7,5% des in der Kreislaufperipherie zirkulierenden Noradrenalins aus dem Nebennierenmark stammen. Die Adrenalin- und Noradrenalinkonzentration im Nebennierenvenenblut bei Patienten mit essentieller Hypertonie war nicht höher als bei Personen mit normalem Blutdruck.
    Notes: Summary In 10 human subjects (5 with normal blood pressure, 4 with essential hypertension, 1 with renal hypertension) local catecholamine levels in blood of suprarenal vein, renal vein, inferior vena cava and iliac vein were determined by a radioenzymatical method. The following concentrations per ml plasma were found: (1) in the suprarenal vein of the left adrenal gland 13.87±8.18 ng adrenaline and 2.82±1.82 ng noradrenaline; (2) in the left renal vein, after confluence of suprarenal with renal blood, 1.44±1.13 ng adrenaline and 0.37±0.18 ng noradrenaline; (3) in the inferior vena cava, cranial of both renal veins, 0.16±0.10 ng adrenaline and 0.30±0.10 ng noradrenaline; (4) in periphery, as in the iliac vein, the plasma adrenaline concentration was only 0.09±0.03 ng/ml, corresponding to 1/154 of suprarenal vein blood concentration; the noradrenaline concentration in iliac vein was 0.24±0.14 ng/ml plasma. Assuming that noradrenaline released from the adrenal medulla follows the same distribution and elimination mechanisms as adrenaline, it was calculated that only 7.5% of noradrenaline found under basal conditions in the periphery of the circulation, originates from the adrenal medulla. The adrenaline and noradrenaline concentration in blood of suprarenal vein of patients with essential hypertension was not higher than the concentrations found in subjects with normal blood pressure.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-1912
    Keywords: Monoamine Oxidase ; Irreversible Enzyme Inhibition ; Rates of Recovery from Inhibition ; Enzyme Protein Turnover ; Tranylcypromine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. After irreversible inhibition of monoamine oxidase (MAO) in rats with hydrazine derivatives (3-amino-2-oxazolidinone, furazolidone, benmoxine) and the non-hydrazine pargyline, recovery of enzyme activity occurred at rates which were characteristic for the organ investigated and independent of the chemical structure of the irreversible inhibitor. The respective half times were the same in homogenates and in mitochondria and amounted to about 10 days in the brain and 3 to 4 days in the liver; in the small intestine, mucosal MAO activity recovered with a half time of 0.5 days, whereas in the residual intestinal layers a half time of about 4 days was found.\3-Tranylcypromine is not an irreversible inhibitor: the half times of MAO recovery were 3.6 days in the brain and 2.4 days in the liver. Thus, long duration of inhibition and organ-specific half times of recovery of MAO inhibition are characteristic features of irreversible inhibitors. 2. When mitochondrial protein was labelled by i.v. injection of 14C-leucine, specific radioactivity declined with a half time of 9.4 days in the brain and 4.0 days in the liver; for the intestinal mucosa and for the residual intestinal layers, a half time of 0.5 and 4.4 days, respectively, was found. As these values are nearly identical with those found for the rates of MAO recofery after irreversible inhibition, the assumption is supported that irreversibly inhibited MAO must be replaced by newly synthetized enzyme. Vice versa, the rates of MAO recovery after irreversible inhibition seem to reflect the rates of mitochondrial protein turnover. Measurements of the rate of recovery of irreversibly inhibited MAO activity may therefore be useful to determine the turnover of the enzyme protein.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...