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  • 1
    Electronic Resource
    Electronic Resource
    Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study (1995)
    Springer
    Psychopharmacology 117 (1995), S. 371-378 
    Details
    ISSN: 1432-2072
    Keywords: Clozapine ; Desmethyl-clozapine Serum concentration ; Side effects ; EEG Schizophrenic patients ; Cross-sectional study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and outpatients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228–425) mg/24 h (range 100–700). There was a weak positive correlation between doses and the BPRS total score (r=0.44,P〈0.05). The median S-Cloza was 1076 (706–1882) nmol/l (range 196–5581 corresponding to 64–1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r=0.90;P〈0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r=0.43;P〈0.05). The score values of the UKU Side Effect Scale were weakly (r=0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246112
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of 3,N,N′-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain (1992)
    Springer
    Journal of neural transmission 88 (1992), S. 177-185 
    Details
    ISSN: 1435-1463
    Keywords: Phenylpiperazine ; monoamine uptake ; NA ; DA ; 5-HT ; MAO ; phenylethylamine ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The diastereomers of 3,N,N′-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2R, 3R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2S, 3S)-TPP was least potent. In contrast, the (2S, 3S)- and (2 S, 3R)-diastereomers of TPP were more potent than (2R, 3R)- and (2R, 3S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244731
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    Paper (German National Licenses)
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