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  • 11
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 215-220 
    ISSN: 1432-1041
    Keywords: hypertension ; muzolimine ; mild renal functional impairment ; diuretic treatment ; body sodium ; catecholamines ; cardiovascular pressor responsiveness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen patients with mild impairment of renal function (glomerular filtration rate 65±5 ml/min: m±SEM) and hypertension (168/105±6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p〈0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35±2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p〈0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.
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  • 13
    ISSN: 1432-1041
    Keywords: prizidilol ; vasodilator ; hypertension ; beta blocker ; plasma renin ; aldosterone ; catecholamines ; acetylator type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (〈107 mmHg) from 3 to 7 h and was still below predose levels 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to 〈95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidilol.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 2 (1969), S. 23-26 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Attempts to treat Parkinson's disease with L-DOPA have led to a turning-point in the therapy of this disease, akinesia responding particularly well to this drug. The high doses of L-DOPA which are necessary to improve the clinical condition are not free from disadvantages. The combination with the decarboxylase inhibitor Ro 4-4602 allows a considerable reduction of the effective dose of L-DOPA, the results being equally satisfactory. A pilot study involving 10 treated patients was conducted to compare the effects of L-DOPA alone and of the combination with Ro-4-4602. Objective assessment was obtained with the help of psycho-physiological senso-motor tests which are briefly described.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 71-75 
    ISSN: 1432-1041
    Keywords: cephalosporin ; ceftriaxone ; protein binding ; non-linear pharmacokinetics ; intravenous injection ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of total (bound and unbound) and free (unbound) ceftriaxone in six healthy volunteers after intravenous injection of 39 were compared with low-dose data from a previous study. The dose-dependent behaviour of total drug was considerably more pronounced after the 3 gram dose. In contrast, total body clearance (Cl S F =258 ml/min), renal clearance (Cl R F =170 ml/min) and volume of distribution (V D(β) F =168 l) of free (unbound) drug did not differ from the data reported earlier. There was no significant change in biological half-life (t1/2(β)=7.8 h) or in the fraction excreted unchanged in urine (fu=0.67).
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  • 16
    ISSN: 1432-1041
    Keywords: cianergoline ; hypertension ; dopaminergic agonist ; renin angiotensin aldosterone ; lipid metabolism ; benign essential hypertension ; side-effects ; prolactin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cianergoline is a new dopaminergic agonist with a predominant cardiovascular action. Its effects on blood pressure, the renin-angiotensin-aldosterone axis, the sympathetic nervous system and lipid metabolism were assessed in 20 patients with benign essential hypertension. Cianergoline given in increasing doses for 4 weeks (maximum daily dose 12±2 mg (SD)) and placebo both caused a slight decrease in arterial pressure, (from 159/104 to 152/98 mm Hg and from 154/104 to 149/103 mm, respectively; difference not significant). Supine and upright plasma renin activity, plasma aldosterone, norepinephrine, epinephrine and dopamine levels, urinary catecholamine excretion rates as well as serum prolactin, low and high density cholesterol and triglyceride concentrations were not changed after cianergoline or placebo. Total serum cholesterol and triglyceride levels decreased significantly after placebo, but were unchanged after cianergoline. 3 out of 10 patients in the cianergoline group complained of nausea. The findings indicate that the new dopaminergic agonist cianergoline exerts only a mild blood pressure lowering effect in patients with essential hypertension and does not modify the release of prolactin, lipid metabolism or the basal activity or postural responsiveness of the renin-angiotensin-aldosterone axis and of the sympathetic nervous system.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 39-45 
    ISSN: 1432-1041
    Keywords: Parkinsonism ; DOPA Decarboxylase inhibitor ; Benserazide ; L-DOPA ; Pharmacokinetics ; Tissue distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 14C-labelled benserazide was administered to six patients with parkinsonism and total radioactivity was measured in the plasma, urine and faeces. Three patients received benserazide both orally and intravenously, while three other patients received benserazide orally alone and together with L-DOPA (= MADOPAR®). Plasma levels did not follow first-order kinetics, but indicated rapid absorption of an oral dose. Following intravenous and oral administration, excretion of radioactivity was 88.7 and 57.7% respectively in the urine, 10.1 and 30.7% respectively in the faeces. L-DOPA slightly increased the absorption of benserazide. Following the administration of an oral dose to rats benserazide related radioactivity was distributed almost entirely outside the brain. The drug therefore appears to be suitable for blocking extracerebral decarboxylase whilst leaving the intra-cerebral enzyme almost unaffected.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 3 (1971), S. 172-175 
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; L-DOPA ; decarboxylase inhibitor ; psychomotor performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty patients with parkinsonism were given a series of psychomotor tests before and during treatment with L-DOPA combined with a decarboxylase inhibitor. This new therapeutic combination produced greater improvement of performance in simple motor activities than in tests which required an ordered sequence of movements or decision taking. It is concluded that L-DOPA combined with a decarboxylase inhibitor acts mainly on efferent motor pathways rather than on afferent sensory pathways, or on the central nervous structures responsible for the programming and planning of actions.
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  • 19
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effect of angiotensin II (A II) on the release of catecholamines was examined on 6 anesthetized dogs. Subpressor (5 ng/kg/min) and high pressor doses (1000 ng/kg/min) of A II were infused into an internal carotid artery. While subpressor doses of A II caused no increase of the catecholamine excretion, both epinephrine and norepinephrine excretion increased considerably under pressor doses of A II. The increase of the epinephrine excretion was statistically significant (p〈0,05). Considering the partly contradictory results of other authors, the discussion deals mainly with problems of dose, mode and site of action of A II and the influence of anesthesia. Finally, a possible significance of our results for the pathogenesis of special types of arterial hypertension is discussed.
    Notes: Zusammenfassung Die Wirkung von Angiotensin II (A II) auf den Katecholaminhaushalt wurde an 6 narkotisierten Hunden geprüft. Dabei wurden subpressorische (5 ng/kg/min) und stark pressorische (1000 ng/kg/min) Angiotensin-Dosen, denen jeweils Infusionen von 0,9%igen NaCl-Lösungen vorausgingen, in die Arteria carotis interna infundiert. Während unter subpressorischen A II-Infusionen keine Steigerung der Katecholaminausscheidung beobachtet werden konnte, stieg die Adrenalin- und Noradrenalinexkretion unter der pressorischen A II-Gabe deutlich an. Die Erhöhung der Adrenalinausscheidung war dabei statistisch signifikant (p〈0,05). Die Ergebnisse werden im Zusammenhang mit den zum Teil unterschiedlichen Befunden anderer Autoren besprochen, wobei vor allem Fragen des Angriffspunktes und des Wirkungsmechanismus von A II, der A II-Dosierung und der Narkose erörtert werden. Schließlich wird diskutiert, welche Bedeutung die Befunde im Hinblick auf die Pathogenese besonderer Hypertonieformen besitzen können.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 457-466 
    ISSN: 1432-1440
    Keywords: Diabetes Mellitus ; Autonome Neuropathie ; Autonome Funktionstests ; Renin ; Katecholamine ; Diabetes mellitus ; Autonomic neuropathy ; Autonomic function tests ; Renin ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Quantitative assessment of signs or symptoms of neuropathy, and the beat-to-beat variation, valsalva, orthostasis, handgrip and cold pressor tests, and measurements of plasma renin and catecholamine excretion rate were performed in 23 diabetic patients and 10 age-matched normal subjects. Significant inverse correlations were found between the clinical score and the beat-to-beat variation (a test of efferent vagus function) (r=-0.72,P〈0.0005) or the pressor response to handgrip (possible test of efferent sympathetic integrity (r=-0.55,P〈0.005) or the values of both tests combined (r=-0.79,P«0.0005); but not with the other measured parameters. Beat-to-beat variation was abnormal in all 9 diabetics with increased and in 9 of 14 with normal clinical score, whereas only seven and one patient from these subgroups, respectively, had an abnormal Valsalva ratio. The pressor response to handgrip was only slightly reduced in the diabetic patients, with greater tendency in those with abnormal clincal score. Additional possible indices of adrenergic dysfunction such as the pressor response to cold stimulus, plasma renin levels and noradrenaline or adrenaline excretion rates did not differ significantly between normal subjects and diabetics. These findings demonstrate a greater prevalence of parasympathetic as compared to sympathetic impairment in diabetic autonomic neuropathy; the beat-to-beat variation was the most sensitive among the tests used. An assessment of clinical evidence combined with non-invasive functional procedures such as the beat-to-beat variation and handgrip tests provide a valuable and easy to perform tool in the evaluation of diabetic neuropathy.
    Notes: Zusammenfassung Bei 23 Diabetikern und 10 Normalpersonen wurden die klinischen Symptome und Befunde einer Neuropathie quantitativ analysiert, und der Beat-to-Beat-Variations-Test, der Valsalva-Versuch, die Orthostase-, Handdruck- und Kälte-Pressor-Tests sowie Bestimmungen von Plasmarenin und Katecholaminexkretionsraten durchgeführt. Die klinische Punktzahl korrelierte invers mit der Beat-to-Beat-Variation (Test der efferenten Vagusfunktion) (rΞ-0,72,P〈0,0005), mit der Blutdruckreaktion während manuellem Pressen (möglicher Test des efferenten Sympathicus) (r=-0,55,P〈0,005), sowie noch besser mit beiden Tests zusammen (r=-0,79,P«0,0005). Mit den übrigen Parametern korrelierte die klinische Punktzahl nicht. Die Beat-to-Beat-Variation war bei allen 9 Diabetikern mit erhöhter und bei 9 von 14 mit normaler klinischer Punktzahl abnormal, die Valsalva-Ratio bei 7 bzw. 1 Patient dieser Subgruppen. Die pressorische Antwort auf manuelles Pressen war bei den Diabetikern nur gering abgeschwächt, etwas ausgeprägter bei der Subgruppe mit erhöhter klinischer Punktzahl. Weitere mögliche Parameter der sympathischen Funktion wie Kälte-Pressoreffekt, Plasmarenin- und Urin-Adrenalin-und Noradrenalin-Werte unterschieden sich zwischen Normalpersonen und Diabetikern nicht signifikant. Diese Befunde weisen auf eine größere Prävalenz von parasympathischen gegenüber sympathischen Ausfällen bei autonomer diabetischer Neuropathie hin. Dabei war die Beat-to-Beat-Variation in dieser Serie der empfindlichste Test. Eine klinische Analyse kombiniert mit nicht-invasiven Funktionstests wie Beat-to-Beat-Variation und Handdruck-Test, sind nützliche und auch in der Praxis anwendbare Hilfsmittel bei der Untersuchung einer diabetischen Neuropathie.
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