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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) labeled with three deuterium atoms was used to study the turnover and fate of HMMA following intravenous injection. Five healthy men were given a pulse dose of 5.0 μmol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 × 10% (mean ± SD). No conversion of HMMA t o 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 ± 0.22 h. The apparent volume of distribution was 0.36 ± 0.11 L/kg. The production rate or body turnover was 1.27 ± 0.51 μmol HMM/h and urinary excretion rate was 0.82 ± 0.22 μmol/h. These results show that HMMA is turning over rapidly in a relatively small volume of distribution and that, unlike HMPG, it is an end metabolite of norepinephrine in man.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with three deuterium atoms was used to study the disposition of peripherally administered HMPG. Five healthy men were given an intravenous pulse dose of 4.3 μmol of labelled HMPG and subsequent plasma and urine levels of endogenous and labelled HMPG as well as those of 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) were determined by gas chromatography-mass spectrometry, using selected ion detection. Approximately 40% of the injected amount of deuterium-labelled HMPG was recovered in the urine as HMMA and another 40% was eliminated as HMPG conjugates. Thus, the HMPG formed from norepinephrine either in the central or peripheral nervous system undergoes both conjugation and extensive oxidation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 6 (1976), S. 498-504 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 255 (1975), S. 418-419 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In preliminary experiments female NMRI mice (body weight at end of experiment 27 + 0,5 g) were pretreated with BSA-morphine once a week for 6 months as described by Berkowitz and Spector1. It was found, however, when the antiserum properties were tested in vitro, that to achieve a 50% displacement ...
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  • 5
    ISSN: 1573-8744
    Keywords: amphetamine pharmacokinetics ; amphetamine-induced euphoria and dysphoria ; amphetamine blocking agents ; α-methyltyrosine ; effects of urinarypH ; amphetamine metabolites ; p-hydroxyamphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Intravenous administration of 200 mg of amphetamine to 12 human subjects induced a stage of euphoria noticeable for 10–12 hr followed by signs of dysphoria which were noticeable early but reached a maximum at 14 hr after injection and remained for 48 hr. The subjective effects of amphetamine could be blocked by α-methyltyrosine. The duration of this antiamphetamine action was more than 24 hr. Pharmacokinetic studies in amphetamine- dependent subjects using large intravenous doses were undertaken to relate measurable pharmacokinetic parameters to the clinical manifestations of amphetamine abuse such as paranoid psychosis and development of tolerance. Subjects having an acidic urine exhibited a relatively mild psychosis, while the psychotic symptoms were aggravated in patients with an alkaline urine. The plot of plasma half- life against mean urinary pH during the first 20 hr yielded a striking correlation. For every increase in unit of urinary pH, there was an increase of plasma half-life of about 7 hr. The intensity of the psychosis in patients having an alkaline urine appeared to be dependent on the metabolite levels rather than on the plasma levels of unchanged drug. A pH-dependent excretion of p-hydroxyamphetamine was noted, and it was found that this metabolite was eliminated slower than the parent compound. The second major metabolite was norephedrine.
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A double isotope labelling technique was used to simultaneously determine the in vivo turnover rates of 4-hydroxy-3-methoxyphenylglycol (HMPG) and 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) and the rate of HMPG oxidation to HMMA. Six healthy men were given intravenous injections of [2H3]HMPG and [2H6]HMMA and their plasma and urine samples analysed by gas chromatography-mass spectrometry (GC/MS) for the protium and deuterium species. HMPG and HMMA production rates were calculated by isotope dilution. The rate of HMPG oxidation to HMMA was obtained from the fraction of [2H3]HMPG recovered as [2H3]HMMA. The results showed that the entire production of HMMA, 1.11 ± 0.21 μmol/h (mean ± SE), could be accounted for by oxidation of HMPG, 1.49 ± 0.31 μmol/h. In another experiment designed to avoid expansion of the HMPG body pool, a tracer dose of [14C]HMPG was given to the same subjects. The levels of [14C]HMPG and [14C]HMMA were measured in urine after extraction and separation by thin layer chromatography. Urinary excretion of endogenous HMPG and HMMA was determined by GC/MS. The results showed that the endogenous HMMA fraction of the total HMPG and HMMA urinary excretion rate, 0.57 ± 0. 04, was the same as the fraction of [14C]HMPG oxidized to [14C]HMMA, 0.62 ± 0.01. Thus, HMPG is the main intermediate in the metabolic conversion of norepinephrine and epinephrine to HMMA in man.
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  • 7
    ISSN: 1432-2072
    Keywords: Propranolol ; Opiate Addiction ; Abstinence Syndrome ; Narcotic Blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two doubleblind placebo controlled experiments designed to elucidate the alleged narcotic blocking effect of propranolol were performed. In the first experiment, propranolol 40 mg or 20 mg was given together with methadone during the acute withdrawal phase of opiate addiction. The second experiment assessed whether 10 mg of propranolol, given 2 hrs before 30 mg of morphine i.v., reduced the euphoric effects of the latter drug. In none of the experiments could narcotic blocking effects be detected. The group receiving 40 mg propranolol during detoxification exhibited the highest proportion of patients staying for the whole prescribed detoxification period.
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  • 8
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A mass fragmentographic method for simultaneous measurement of unlabeled and deuterium labeled methadone in human plasma is described. This specific method has a lower sensitivity of about 16 pmol/ml with a coefficient of variation of less than 4%. The usefulness of the method was evaluated in studies on opiate dependent subjects undergoing methadone maintenance treatment. In one application methadone-d3 was given as a pulse dose during continuous treatment with unlabeled methadone and plasma levels of both species followed by mass fragmentography. The method will be of value in the study of methadone pharmacokinetics in the steady state and in other in vivo situations where multiple drug pools must exist.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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