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  • Learning  (1)
  • inhibitor  (1)
  • 1
    ISSN: 1569-8041
    Schlagwort(e): inhibitor ; lipoxygenase ; pancreatic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose:Primary objective was to determine response rate ofpatients with advanced pancreatic cancer to a novel lipoxygenase andthromboxane A2 synthetase inhibitor (CV6504); secondary objectives includedestimation of pharmacokinetics of CV6504, target-enzyme inhibition, safety andtolerance, quality of life and survival. Patients and methods:Thirty-one patients with advanced pancreaticcancer were planned to receive CV6504, 100 mg TDS, orally for three months,at which point CT scans were performed to assess therapeutic response rates.Steady state concentrations of CV6504 and thromboxane B2 (an indirect measureof thromboxane A2 synthetase (TA2S) inhibition) were made. Of the31 patients entered into the study, 23 were considered fully evaluable forresponse. Results:The drug was well tolerated with few side effects; nopartial or complete responses were seen, but 10 patients had stable diseaseat 3 months; quality of life was maintained during therapy; mean CV6504 steadystate plasma concentrations of 14 ± 6 ng/ml resulting in 75 ±18% inhibition of TA2S were achieved; median-survival timefor all patients considered eligible for assessment of efficacy was 36.6 weeksafter the initial dose of study medication. The actuarial one-year survivalwas approximately 25%. Conclusion:CV6504 inhibits its target enzyme in vivo,maintains stable disease in 32% of evaluable patients and is welltolerated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 125 (1996), S. 220-230 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Morphine ; Drug tolerance ; Behavior ; Learning ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Experiments examined how learning processes modulate tolerance to discriminative stimulus effects of morphine. Rats were trained to discriminate saline and 3.2 mg/kg morphine, and the doses of morphine required to mimic the training dose were determined before, during and after repeated treatment with saline or high doses of morphine (10 mg/kg, b.i.d.). In one set of experiments, training was either suspended or continued with saline and the original training dose during a 2-week treatment regimen. When training was suspended, high-dose morphine treatment increased the dose of morphine required for stimulus effects approximately 3-fold. Tolerance persisted 2 days after treatment ended, but disappeared within 7 days. In contrast, continued training with saline and 3.2 mg/kg morphine during high-dose treatment both attenuated development of tolerance and transferred control to lower doses. Transfer of control to lower doses appeared conditional upon recent termination of high-dose treatment, as it disappeared within 7 days. Treatment with saline did not change the doses of morphine required for stimulus effects under either training condition. A final experiment examined whether high-dose treatment could transfer control to higher doses of morphine. The treatment dose of 10 mg/kg morphine itself was used as the training dose during a 2-week treatment regimen. The dose of morphine required for stimulus effects increased 2- to 4-fold during treatment, but quickly returned to control values when treatment ended. These results extend previous findings that conditioning and pharmacodynamic processes jointly regulate development of tolerance to discriminative effects of morphine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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