Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Modifying quinolone antibiotics yields new anxiolytics (2004)
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 31-32 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Patients taking fluoroquinolone antibiotics such as norfloxacin exhibit a low incidence of convulsions and anxiety. These side effects probably result from antagonism of the neurotransmitter γ-aminobutyric acid (GABA) at the brain GABAA receptor complex (GRC). Modification of norfloxacin ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm967
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Preparation, Purification, and Characterization of a Reversibly Lipidized Desmopressin with Potentiated Anti-Diuretic Activity (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1674-1679 
    Details
    ISSN: 1573-904X
    Keywords: desmopressin ; palmitic acid ; conjugate ; anti-diuretic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To prepare and characterize a reversibly lipidized dipalmitoyl desmopressin (DPP), and to compare its anti-diuretic efficacy and biodistribution with that of unmodified desmopressin (DDAVP). Methods. Dithiothreitol (DTT) was used to reduce the intramolecular disulfide bond in DDAVP, and the reduced DDAVP was treated with a thiopyridine-containing disulfide lipidization reagent, Pal-CPD. The product, DPP, was purified by acid precipitation and, subsequently, by size-exclusion chromatography. Reversed-phase HPLC was used to analyze the purity and to evaluate the hydrophobicity of the product. Mass spectrometry was employed to characterize its molecular structure. The biological activity of DPP was demonstrated by the anti-diuretic effects in vasopressin-deficient Brattleboro rats. Preliminary pharmacokinetic and biodistribution studies of intravenously injected DDAVP and DPP were carried out in CF-1 mice. Results. DDAVP was readily reduced by a 2-fold molar excess of DTT at 37°C for 0.5 hr. DPP was formed by the reaction of reduced DDAVP with Pal-CPD. Each DPP molecule contains two palmitic acid moieties, which link to the peptide via two disulfide bonds. After acid precipitation and size-exclusion chromatography, the purity was found to be approximately 95%, and the overall yield was 57%. When DPP was administered subcutaneously to Brattleboro rats, the potency of the anti-diuretic activity of DDAVP was enhanced to more than 250-fold. The plasma concentration of intravenously injected DDAVP in mice decreased rapidly during the first 20 min and followed by a slow elimination rate. However, in DPP administered mice, the plasma concentration actually increased in the first 20 min, followed by a slow elimination with a rate similar to that in DDAVP-injected mice. The regeneration of DDAVP was detected in the plasma of mice treated with DPP. Studies of the organ distribution in mice indicated that the liver retention of DPP was longer than that of DDAVP. On the other hand, the intestinal excretion of DPP was significantly less than that of DDAVP. Conclusions. The 250-fold increase of the anti-diuretic potency in DPP is most likely due to a slow elimination and prolonged tissue retention, together with the regeneration of active DDAVP, in the animals. Our results indicate that reversible lipidization is a simple and effective approach for improving the efficacy of many peptide drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018929312715
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Identification of new metabolites of ifosfamide in rat urine using ion cluster techniquePresented at the 85th annual Meeting of American Association of Cancer Research, April 1994, San Francisco, California. (1995)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 30 (1995), S. 675-683 
    Details
    ISSN: 1076-5174
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Metabolism of the anticancer drug ifosfamide was investigated in Sprague-Dawley rats. Along with four known metabolites, namely N2-dechloroethylifosfamide, N3-dechloroethylifosfamide, alcoifosfamide and isophosphoramide mustard, four new urinary metabolites were identified utilizing combined techniques of chemical modification/derivatization, capillary gas chromatography/chemical ionization mass spectrometry (ammonia), deuterium-labeling/ion cluster analysis and chemical synthesis. Secondary metabolites of N2-dechloroethyl and N3-dechloroethylifosfamide formed by 4-hydroxylation, i.e. 4-hydroxy-N2-dechloroethylifosfamide and 4-hydroxy-N3-dechloroethylifosfamide, respectively, and their subsequent decomposition product, N-dechloroethyliso-phosphoramide mustard, were identified. Secondary dealkylation pathways of N2-dechloroethylifosfamide and/or N3-dechloroethylifosfamide were also demonstrated through characterization of N2,3-didechloroethyl ifosfamide. The key active metabolite of ifosfamide, 4-hydroxyifosfamide, was characterized as a cyanohydrin adduct for the first time.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jms.1190300504
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Comparison of Pharmacokinetic Parameters of a Polypeptide, the Bowman-Birk Protease Inhibitor (BBI), and Its Palmitic Acid Conjugate (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1373-1377 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; polypeptide ; BBI ; palmitic acid ; conjugation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The alteration of the pharmacokinetic parameters of the poly-peptide BBI through conjugation with palmitic acid was examined. Methods. 125I-BBI or l25I-Pal-BBI was administered iv to 6 week old CF-1 mice at a dose of 3mg/kg. The mice were sacrificed at 5, 10, 20, 60, 120, 240, 360, and 480 min and the total radioactivity was determined for blood and each organ. The blood was analyzed on a Sephadex G-50 size-exclusion column to determine the amount of intact polypeptide present in the blood. From the amount of intact polypeptide at each time point, the pharmacokinetic parameters were determined. Results. By conjugating three palmitic acids to each BBI molecule, the area under the curve (AUC) and mean residence time (MRT) increase by a factor of 10.8 and 2.8, respectively. There was also a difference in the organ distribution between the two treatments; while 125I-BBI was rapidly cleared from the kidneys, l25I-Pal-BBI was predominantly to the liver. Subsequent studies suggested that the binding of the conjugate to non-albumin serum proteins was most likely the cause of the altered pharmacokinetics. Conclusions. The residence time in the blood and the lipophilicity of BBI were increased upon conjugation with palmitic acid through a reversible disulfide linkage. Pharmacokinetic studies showed an increase in the AUC and a decrease in kidney clearance in palmitic acid conjugates, indicating a potential increase of the therapeutic efficacy of the polypeptide drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016078118033
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...