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  • 1
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Systolic pressor effects after i.v. injection of tyramine (TA) were recorded in 13 patients before and during treatment with nortriptyline (NT) in doses of 1.4–5 mg/kg/day for 3–4 weeks. After NT a several fold decrease in the responsiveness to TA occurred. Patients given the same dose of NT showed markedly different decreases in the responsiveness to TA. There was no correlation between the blockade of the TA pressor effects and the dose of NT employed but there was an excellent correlation between the blockade and the plasma level of NT (p〈0.001 and p〈0.005 respectively). TA pressor effects were not changed in a small control group of depressed patients after treatment with E.C.T. The relationship between kinetics and effects of tricyclic antidepressants is discussed. The steady-state plasma level of NT seems to be an important determinant of its effects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Antidepressant ; nortriptyline ; tyramine ; noradrenaline uptake ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This report describes a phase I clinical trial of a new tricyclic imipramine analogue (Leo 640) with a hydrogen atom in one of the N-methylgroups substituted by a p-chlorobensoyl. To get an objective assessment of the effects of Leo 640 we utilized the fact that tricyclic antidepressants inhibit the uptake of tyramine (thereby blocking its indirect sympathomimetic effects) and noradrenaline into peripheral adrenergic nerves. Dose-response (systolic pressor effects) curves for tyramine (TA) were established before and during treatment with Leo 640. Adrenergic nerves from the rat iris were incubated in the patient's plasma drawn immediately before the TA tests. The inhibitory effect of the endogenous plasma level of Leo 640 (and/or its metabolites) on the uptake of3H-noradrenaline (3H-NA) in these nerves was then determined. — Leo 640 was given orally in successively increasing doses (up to 1.1–5.6 mg/kg/day) to fifteen patients with various forms of depression. The duration of treatment was usually 3–4 weeks. Leo 640 caused a blockade of TA- pressor responses. Plasma of all treated patients inhibited the uptake of3H-NA in the rat iris. The results in the two tests were reasonably well correlated (p〈0.01). — The results in the TA- and “rat-iris” tests were compared with those obtained with nortriptyline (NT) in the same dose-range in nine other patients. In comparison with NT, Leo 640 had a more pronounced inhibitory effect on TA-responsesin vivo than of3H-NA uptake in adrenergic nervesin vitro. A possible explanation might be that Leo 640 has an α-receptor blocking effect. — For both Leo 640 and NT, poor correlations were found between the doses (mg/kg) used and the objective effects, when different patients were compared, probably due to marked interindividual differences in pharmacokinetics. — It is concluded that the dose-range of Leo 640 should be similar to that of NT in terms of the effects onperipheral adrenergic neurons.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 2 (1970), S. 68-71 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 40 depressed patients treated with 25 or 50 mg nortriptyline (NT) t. i. d. for 3 weeks the following circulatory variables were observed prior to and during drug therapy: heart rate and blood pressure at rest (in supine and standing positions), working capacity, ECG at rest and during exercise on a bicycle ergometer. During administration of NT the heart rate increased significantly at rest in both supine and standing positions, but the orthostatic heart rate reaction remained unchanged. Diastolic blood pressure in the supine position rose slightly; in the standing position the pretreatment increase in diastolic pressure was abolished. The positive chronotropic effect did not correlate with the steady-state plasma level of NT. In one patient on NT a right bundle branch block appeared during the work test; in the remaining 39 patients the ECG records at rest and during exercise showed no adverse effects of NT.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 55 (1999), S. 619-624 
    ISSN: 1432-1041
    Keywords: Key words Computerised electrocardiogram ; Heart rate changes ; Influence of food
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To study the influence of food intake on electrocardiogram (ECG) variables (heart rate, QT-, QTc-, PR-intervals, QRS-time) and morphological alterations of the T-waves in 12 healthy male volunteers. Methods: The study was of open, three-period crossover design. On each occasion, all subjects fasted from midnight. During two of the study periods, the subjects were given a standardised meal at 1.5 h and 5.5 h after the baseline assessments, respectively, whereas, during the third period, they remained fasting for the entire study period of about 9 h. ECG and blood pressure were recorded at baseline and thereafter every hour for 8 h. Results: No ECG changes were observed following the fasting condition, whereas a clear change in ECG and an increased heart rate were recorded in response to the meal intake during the other two periods. The most prominent ECG effect was the change in the size and shape of the T-waves, which were described as flattened to biphasic and, occasionally, negative. These alterations were most pronounced in the precordial leads V4 to V6 in the ECG recording immediately following the meal intake, with a gradual return to baseline conditions over 4–5 h. Moreover, a transient increase of supine systolic blood pressure was also recorded in response to the meal intake. Conclusions: The intake of a meal can cause clear and consistent ECG changes in healthy male subjects, comprising increases in heart rate as well as alterations in the size and shape of the T-waves (flattened to biphasic and, occasionally, negative). Also, a post-meal increase in the supine systolic blood pressure was recorded.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Albumin excretion rate ; angiotensin converting enzyme inhibitor ; blood pressure ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of enalapril on albumin excretion rate was studied in two groups of age- and sex-matched Type 1 (insulin-dependent) diabetic patients, aged 15–20 years, with persistent microalbuminuria 〉20 μg/min. Group 1 contained six patients with systolic blood pressure ≥ 75th percentile for age and sex, group 2 six normotensive patients. Enalapril (10–20 mg/day) was given for six months. Albumin excretion rate, glomerular filtration rate, renal plasma flow, blood pressure at rest and during exercise, and angiotensin converting enzyme activity were measured before, after three weeks' and six months' treatment and six months after treatment withdrawal. Albumin excretion rate decreased in all patients after three weeks' (mean decreases 55% in group 1, 65% in group 2) and six months' treatment (35% in group 1, 61% in group 2). Systolic blood pressure remained unchanged in both groups. Diastolic pressure was reduced after three weeks in group 1 (p=0.001). No reduction in increment in systolic pressure during exercise test occurred in any group during treatment. Angiotensin converting enzyme activity decreased in all patients after three weeks (p=0.001) and six months (p=0.003). This correlated to the decrease in albumin excretion rate after three weeks (r=0.79, p=0.05) and six months (r=0.59, p=0.04). HbA1c, mean blood glucose and glomerular filtration rate remained unchanged during the study in both groups. Renal plasma flow tended to increase after three weeks' and six months' treatment in group 2 (p=0.06, respectively) but not in group 1. Filtration fraction decreased after three weeks (p=0.04) only in group 2. In conclusion, enalapril reduces the albumin excretion rate in adolescent diabetic patients with or without elevated blood pressure. This reduction was not accompanied by a decreased systemic pressure but rather by a fall in filtration fraction in normotensive patients, indicating a direct effect, irrespective of the antihypertensive, on intraglomerular pressure.
    Type of Medium: Electronic Resource
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