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  • 1
    ISSN: 1432-0533
    Keywords: Fluorescence Histochemistry ; Sympathetic Denervation ; Periarterial Nerve Stimulation ; Regenerating Adrenergic Nerves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After sympathetic denervation of the guinea-pig distal colon the time course and the relationship between morphological and functional changes were studied, by using the fluorescence method and by evaluating the response of longitudinal muscle to periarterial nerve stimulation. The inhibitory response to sympathetic nerve stimulation was completely abolished 48 h after denervation. Tissue catecholamines can no longer be detected in either the intramural vessels or in the intramural plexuses 96 h after denervation, and in no preparation could they be observed again until 24 days after denervation. After 30 days catecholamines stores slowly began to reappear and were completely restored only 100–120 days after denervation. During the whole period of reinnervation the response to periarterial nerve stimulation was lacking. The inhibitory effect could be elicited only 130 days after denervation and before the morphological pattern had been completely restored.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: phenobarbital ; propylhexedrine salt ; barbexaclone ; bioavailability ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of the drug as the acid or the propylhexedrine salt (barbexaclone) to 7 normal volunteers. The absorption and elimination parameters were very similar. It was concluded that propylhexedrine did not affect the serum kinetics of PB given as barbexaclone.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Trandolapril ; ACE inhibition ; pharmacodynamics ; duration ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacological activity and safety of the new angiotensin converting enzyme (ACE) inhibitor trandolapril (RU 44570) has been evaluated in ten healthy male volunteers given 2 mg once daily for seven days. Assessment criteria included evaluation of plasma ACE and renin activity and aldosterone levels in the supine and standing positions, monitoring of blood pressure, heart rate and electrocardiogram, routine blood and urine laboratory tests, and evaluation of adverse effects. Plasma ACE activity (both in the supine and standing positions) was significantly lower after the first dose and was almost completely suppressed after 7 days of treatment. Plasma renin activity with the subjects in both positions was significantly increased at the end of treatment. Plasma aldosterone did not vary significantly, except for an increase in the standing position after 7 days of washout. No significant changes occurred in blood pressure, heart rate, electrocardiogram, blood or urine laboratory tests. No adverse effects were reported, in particular, no orthostatic hypotension, cough or episodes of bronchospasm occurred. It is concluded that oral trandolapril 2 mg o.d. is an effective and long-lasting ACE inhibitor with a good safety profile on repeated dosing. Further studies are warranted to investigate its therapeutic application as well as its safety profile after long-term administration.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: biperiden ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics (changes in pupil size and salivary flow) of biperiden following a single oral and intravenous dose were investigated in six normal subjects. After the injection plasma concentrations declined biphasically, with half-times of 1.5 h for the rapid phase and 24 h for the terminal phase. Clearance and apparent volume of distribution were high (12 ml·min−1·kg−1 and 24 l·kg−1 respectively). Absorption was rapid but the systemic availability was incomplete (33%), probably due to first-pass metabolism. Central nervous system (CNS) adverse effects and changes in pupil size were observed after both routes of administration while salivary flow was affected only by the injection.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 135-137 
    ISSN: 1432-1041
    Keywords: phenytoin ; drug interactions ; cimetidine ; inhibition of metabolism ; disposition kinetics ; mixed function oxidases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine on the disposition kinetics of phenytoin was investigated in 7 healthy volunteers. Each subject received a single intravenous dose of phenytoin on two occasions, in the control state, and during concurrent treatment with cimetidine 1200 mg/day for 6 days. A slight but statistically significant decrease both in the rate of elimination and total body clearance of phenytoin was observed during the administration of cimetidine. The effect is probably due to inhibition of metabolism.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 51 (1996), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 32 (1976), S. 1318-1320 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Oxine-5-sulphonic acid inhibits the metabolism of aminopyrine in the rat liver in vitro. The characteristics of this inhibition vary according to whether the oxidativeN-demethylation of the substrate is determined by the formation of the metabolite 4-aminoantipyrine or by the production of formaldehyde.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 239 (1960), S. 475-480 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Schlußfolgerungen und Zusammenfassung Die Befunde stimmen mit denjenigen von Corda überein. Sie stehen im Gegensatz zu den Befunden von Freerksen, welcher eine Spezifität einiger Organe bei der Spaltung des Antibioticums beobachtet hatte. Dieser Unterschied kann zum Teil seine Erklärung in den verschiedenen Konzentrationen des verwendeten Cycloserins (500 bis 1000 γ/cm3 bei den Untersuchungen von Freerksen und 60 γ/cm3 bei den unsrigen) und in der Verschiedenheit der Tierarten, welche verwendet wurden, finden. So hat z.B. Freerksen nachgewiesen, daß die Resorption nach peroraler Verabfolgung bei der Maus äußerstschnell und beim Kaninchen sehr langsam vor sich geht. Die von Freerksen verwendeten hohen Dosen könnten jedoch eine geringfügige Spaltung verschleiern. Die fehlende Spaltung des Antibioticums in durch Hitze enteiweißten Leber-Homogenaten erlaubt die Schlußfolgerung, daß die Spaltung von enzymatischem Charakter ist. Die Derivate des Cycloserins, welche nach der Methode von Jones eine Färbung geben, haben einen intakten basischen Ring: z.B. Monoacetyl-und Desamino-Cycloserin (Jones). Es ist deshalb anzunehmen, daß der fehlenden Reaktion mit Nitroprussid, auf Grund derer wir glauben, daß es zum Abbau gekommen ist, eine Öffnung des Oxazol-Ringes entspricht. Andererseits schließt Conzelmann beim Affen die Bildung des Acetyl-Derivates aus. Nach Freerksen soll es zur Öffnung des Ringes (vielleicht durch eine Cycloamidase) unter Bildung von Serin, Stickstoff, Wasser und Ammoniak kommen. 1. Cycloserin bei einmaligern Verabfolgung zeigt keine besondere Affinität zu den untersuchten Organen. 2. Bei der Ratte wird die gute Resorption von Seiten des Magen-Darm-Traktes bestätigt; die Verteilung des Pharmakons in den Geweben scheint unabhängig von der Art der Verabreichung zu sein. 3. Auch bei wiederholter Behandlung scheint weder eine besondere Organaffinität, noch eine Kumulation aufzutreten. 4. In der Leber findet sich das Antibioticum vorwiegend in der Supernatantschicht der zentrifugierten Homogenate. 5. Unter den verschiedenen Leber-Fraktionen sollen die Mitochondrien die größte Stoffwechsel-Aktivität haben. Es ist nicht möglich, zu entscheiden, ob die geringe Konzentration in den Mitochondrien einer geringen Eindringung des Antibioticums in diese oder einer intensiven Spaltung zuzuschreiben ist. 6. Cycloserin wird außer von der Leber auch von zahlreichen anderen Geweben gespalten: Lunge, Nirer, Gehirn und Muskel.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1912
    Keywords: Enteric neurones ; Acetylcholine release ; Sympathetic denervation ; α2-Adrenoceptors ; Yohimbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentration-effect relationships of noradrenaline, dopamine and clonidine in inhibiting resting and stimulated acetylcholine output have been studied in intact and in sympathetically denervated preparations of guineapig isolated distal colon. 2. The order of potencies for the inhibition of resting acetylcholine release in intact preparations was clonidine 〉 dopamine 〉 noradrenaline while the order of intrinsic activities was noradrenaline 〉 dopamine 〉 clonidine. 3. Sympathetic denervation was able to modify the potency of either clonidine, dopamine and noradrenaline. Noradrenaline was 6 times more potent in inhibiting resting acetylcholine release in denervated than in intact preparations, while clonidine and dopamine underwent a 18-fold and a 11-fold decrease in potency after denervation. The potency of clonidine relative to noradrenaline was 110 in intact preparations and only 1.2 in denervated organs. The intrinsic activities of noradrenaline, dopamine and clonidine were almost unchanged in denervated organs. 4. A dose-dependent facilitatory effect of yohimbine on both the resting acetylcholine output and the peristaltic reflex could be observed in intact but not in sympathetically denervated preparations at concentrations ranging from 2.5×10−8 M to 2.5×10−7 M. 5. Yohimbine was able to counteract the inhibitory effect of dopamine and to remove the inhibitory effect of periarterial nerve stimulation on both acetylcholine release and the peristaltic reflex. 6. Our results are consistent with the existence of a tonic physiological modulation of enteric cholinergic neurones by postganglionic sympathetic fibres. The order of potencies of adrenoceptor agonists and the antagonism by yohimbine is consistent with such a modulation being entirely carried out through α2-heteroceptors. To what extent pre- or post-junctional factors are involved in the denervation-induced effect cannot be established with certainty from our results. However the pattern of denervation-induced potency changes for noradrenaline, clonidine and dopamine and the difference in their intrinsic activities on α2-adrenoceptors strongly suggest the prevalence of prejunctional factors.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 268 (1971), S. 44-58 
    ISSN: 1432-1912
    Keywords: Caerulein ; Cholecystokinin Pancreozymin ; Peristaltic Reflex ; Intestinal Propulsion ; Myenteric Plexus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Caerulein increased the efficiency of the peristaltic reflex both in the large and small intestine. Such an effect could be evidenced by measuring the velocity of propulsion of a solid bolus in the colon and the amount of ejected fluid in the fatigued ileum. The effect on propulsion was related to the concentrations employed and log dose-response curves could be constructed. 2. Caerulein was able to counteract the inhibitory effect of mild cooling (25 to 28
    Type of Medium: Electronic Resource
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