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  • 1
    Electronic Resource
    Electronic Resource
    Effects of Chlorinated Organics on Intermediates in the Heme Pathway and on Uroporphyrinogen Decarboxylase (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 514 (1987), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1987.tb48767.x
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  • 2
    Electronic Resource
    Electronic Resource
    Serotonin and the Pharmacology of Eating Disorders (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 575 (1989), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1989.tb53243.x
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  • 3
    Electronic Resource
    Electronic Resource
    Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Limbic status epilepticus was induced in rats by unilateral 60-min electrical stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1β, interleukin-6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1β (445%), interleukin-6 (405%) and tumour necrosis factor-α (264%) and at 24 h for interleukin-1 receptor antagonist (494%) and inducible nitric oxide synthase (432%). In rats with spontaneous seizures (60 days after status epilepticus), interleukin-1β mRNA was still higher than controls (241%). Immunocytochemical staining of interleukin-1β, interleukin-6 and tumour necrosis factor-α was enhanced in glia with a time-course similar to that of the respective transcripts. Sixty days after status epilepticus, interleukin-1β immunoreactivity was increased exclusively in neurons in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 μg/3 μL) significantly decreased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-α content in the hippocampus measured 18 h after status epilepticus. Thus, the induction of spontaneously recurring seizures in rats involves the activation of inflammatory cytokines and related pro- and anti-inflammatory genes in the hippocampus. These changes may play an active role in hyperexcitability of the epileptic tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00140.x
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  • 4
    Electronic Resource
    Electronic Resource
    NOTES ON XENOBIOTIC METABOLISM (1983)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 407 (1983), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1983.tb47810.x
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  • 5
    Electronic Resource
    Electronic Resource
    From Fenfluramine Racemate to d-Fenfluramine (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 499 (1987), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1987.tb36207.x
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  • 6
    Electronic Resource
    Electronic Resource
    Releasing activities of d-fenfluramine and fluoxetine and fluoxetine on rat hippocampal synaptosomes preloaded with [3H]serotonin (1992)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 345 (1992), S. 1-6 
    Details
    ISSN: 1432-1912
    Keywords: d-Fenfluramine ; Fluoxetine ; [3H]serotonin release ; Synaptosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat hippocampal synaptosomes preloaded with [3H]serotonin and maintained in a superfusion apparatus were exposed for 3 min to d-fenfluramine or fluoxetine. Both drugs evoked a tritium overflow which was reserpine-sensitive requiring the presence of intact synaptic vesicles. However the two drugs displayed different characteristics: 1) the overflow was immediate with dfenfluramine whereas the releasing activity of fluoxetine showed a delay of about 2 min; 2) d-fenfluramine-induced overflow was already apparent at 0.15 μmol/l whereas the minimal effective concentration of fluoxetine was 2.5 μmol/l. Their concentration-effect curves were differently shaped, the effect of d-fenfluramine being saturable at 5–20 μmol/l (EC50 about 1 gmol/l) while no saturation was observed with fluoxetine up to 10 μmol/l; 3) only 1907o of the tritium overflow evoked by fluoxetine (2.5–10 μmol/l) consisted of true [3H]serotonin, compared with 7001o when 0.5 μmol/l d-fenfluramine was used; 4) the releasing action of 0.5 μmol/l d-fenfluramine was completely Ca++-dependent, while at higher dfenfluramine concentrations the Ca++-independent overflow became more important. The fluoxetine induced overflow was mainly. (70010) Ca++-independent; 5) the releasing acitvity of d-fenfluramine was mainly (80%) blocked by the serotonin uptake blockers indalpine, midalcipram and also fluoxetine whereas fluoxetine-induced overflow was insensitive to inhibition of the serotonin carrier. In conclusion, the releasing activity of d-fenfluramine is already present at a very low concentration (0.5 μmol/l) and at this concentration its mechanism of action was Ca++-dependent, together with the requirement of a functional serotonin carrier. These data therefore do not support the hypothesis of a simple. “displacement” of 5-HT from its storage vesicles but suggest an exocytotic release possibly triggered by interaction of d-fenfluramine with intracellular receptors. A direct releasing activity is also shown for fluoxetine, very marked at 5–10 μmol/l; such effect is different from that of d-fenfluramine and is probably due to the overflow of 5-hydroxyindoleacetic acid, formed in the synaptosomes after the fluoxetine-induced “displacement” of serotonin from its storage vesicles. The active concentrations of fluoxetine on serotonin release are compatible with those found in rat brain at doses inducing an anorectic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175461
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  • 7
    Electronic Resource
    Electronic Resource
    Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition (1976)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1976), S. 59-65 
    Details
    ISSN: 1432-1912
    Keywords: Blood platelets ; Serotonin uptake ; Tricyclic antidepressant drugs ; Fenfluramine ; Kinetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent K m values (0.25–2.0 μM). While the apparent K m values were rather similar for human and rat platelets, V max was about 5 times higher in rat than in human platelets. The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibition of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets. Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498840
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of fotemustine and BCNU in plasma, liver and tumor tissue of rats bearing two lines of Walker 256 carcinoma (1991)
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 293-297 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma and tissue pharmacokinetics of fotemustine (diethyl-1-[3-(2-chlorethyl)-3-nitrosoureido]-ethylphosphonate) and BCNU (1,3-bis-[2-chlorethyl]-1-nitrosourea) were investigated in healthy control rats and in animals bearing either the nitrosourea-sensitive line A (W256/A) or the nitrosourea-resistant line B (W256/B) of Walker 256 carcinoma. The antitumor activities of these nitrosoureas were similar following i.v. doses ranging from 10 to 40 mg/kg. For both drugs, the survival of tumor-bearing rats was lower in the W256/B than in the sensitive W256/A line. Some sex differences were observed, female rats being more responsive than males to both drugs. Nitrosourea concentrations were assayed in plasma and tissues by differential pulse polarography so as to assess whether the pharmacokinetics could explain the differences in antitumor activity. The antineoplastic effects of fotemustine seemed to be influenced by its pharmacokinetics. The plasma AUC of the intact nitrosourea was higher in females than in males. Fotemustine was cleared 2–5 times more slowly than BCNU from tumor tissue, and its clearance was higher in W256/B- than in W256/A-bearing rats. This suggests that the antitumor activity in the responsive line might partly be due to longer exposure of the growing tumor to the drug. The distribution volume of both nitrosoureas in plasma was higher in tumor-bearing animals than in healthy controls, indicating that the tumor tissue probably constitutes an additional distribution space.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685537
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  • 9
    Electronic Resource
    Electronic Resource
    Anorectic effect of fenfluramine isomers and metabolites: Relationship between brain levels and in vitro potencies on serotonergic mechanisms (1985)
    Springer
    Psychopharmacology 85 (1985), S. 111-114 
    Details
    ISSN: 1432-2072
    Keywords: Fenfluramine ; Anorectic effect ; Serotonin uptake ; Serotonin release ; 5HT1 binding sites ; 5HT2 binding sites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study of the possible molecular mechanisms of action by which the isomers and metabolites of fenfluramine increase serotonin transmission, leading to anorectic activity, is presented. The actual brain levels of fenfluramine and norfenfluramine isomers after administration of equi-anorectic doses to rats are compared with their potencies in affecting serotonergic mechanisms in vitro. Isomers and metabolites of fenfluramine can have the same pharmacological action by influencing serotonin uptake, release and binding in a quantitatively different manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427333
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of tumor on adriamycin concentration in blood cells (1980)
    Springer
    Cancer chemotherapy and pharmacology 4 (1980), S. 209-212 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative distribution of adriamycin to plasma and blood cells after IV injection of 10 mg/kg was investigated in CD rats bearing intramuscular 256 Walker carcinosarcomas 15 days old. The drug was measured by a fluorimetric procedure and the amount of unchanged compound was separated from metabolites and quantitated by means of a TLC scanning fluorescence technique. In the presence of a tumor much lower hematocrit values are found, with marked anemia and thrombocytopenia associated with leukocytosis. These modified hematologic parameters account for an altered pattern of drug distribution. The low number of blood cells per milliliter results in a smaller amount of drug being present in the cellular fraction, so that more of the compound (even twice as much) is made available in plasma. Changes in adriamycin concentrations per unit volume or cell of each cell type are inversely related to changes in their relative number per milliliter. The only cell fraction where the drug increase per cell or cubic micrometer does not compensate the marked reduction in cell count observed in the presence of tumor is the platelet fraction, in which adriamycin amounts are 25% or less of those observed in the blood of normal rats, indicating that these blood cells become saturated in tumor-bearing animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254021
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