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  • 1
    Electronic Resource
    Electronic Resource
    Effects of psychotropic agents on the physical properties of platelet membranes in vitro (1985)
    Springer
    Psychopharmacology 86 (1985), S. 369-373 
    Details
    ISSN: 1432-2072
    Keywords: Platelet membranes ; Membrane order ; Fluidity ; DPH fluorescence polarization ; Phenothiazines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normal platelet membranes were exposed in vitro to a variety of psychotropic medications commonly used in the treatment of patients with psychiatric disorders. Changes in structural order at the hydrocarbon region of the drug-exposed membranes were determined by steadystate fluorescence polarization measurements employing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Chlorpromazine, an aliphatic phenothiazine, produced a significant increase in DPH fluorescence polarization at concentrations from 2–200 μM. Thioridazine, a piperidine phenothiazine, and three piperazine derivatives, perphenazine, trifluoperazine, and fluphenazine, produced significant increases in this parameter at concentrations from 20–200 μM. The other agents tested, including thiothixene, lithium, antidepressants, anxiolytics, and anticonvulsants, were without effect in the concentration ranges examined. The phenothiazine-induced increase in DPH fluoresence polarization apparently depended on the structure of the phenothiazine nucleus; changes in side-chain structure appeared to modulate this effect, most likely by altering the inherent membrane solubility of the agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432231
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    In vivo effects of psychotropic agents on the physical properties of cell membranes in the rat brain (1985)
    Springer
    Psychopharmacology 86 (1985), S. 365-368 
    Details
    ISSN: 1432-2072
    Keywords: Phenothiazines ; Membrane structural order ; Membrane function ; DPH fluorescence polarization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Marked changes in biophysical properties, including structural order, have been observed in the hydrophobic core of cell membranes exposed to phenothiazines in vitro. In this study, similar changes are reported in vivo in cell membranes from the brains of rats treated with phenothiazines at doses thought to yield tissue concentrations approximating those attained in the clinical treatment of psychiatric patients. The membrane structural order parameter was estimated ex vivo by steady-state fluorescence polarization determinations using 1,6-diphenyl 1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially to the hydrocarbon region of cell membranes. In these preliminary studies, rats received chlorpromazine (20 mg/kg), fluphenazine (1 mg/kg), haloperidol (1 mg/kg), and imipramine (1 mg/kg) in single or multiple dose protocols. As in earlier in vitro studies, exposure to the phenothiazine antipsychotics led to an observed increase in DPH fluorescence polarization ex vivo and a presumed increase in structural order. As predicted from the in vitro experiments, the effect of chlorpromazine was greater than that of fluphenazine, probably because chlorpromazine was given at higher doses. The magnitude of the effects seen was great enough to imply that physiologically significant changes in cell membrane characteristics may be produced in patients receiving phenothiazines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432230
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    A cell membrane correlate of tardive dyskinesia in patients treated with phenothiazines (1986)
    Springer
    Psychopharmacology 88 (1986), S. 230-236 
    Details
    ISSN: 1432-2072
    Keywords: Tardive dyskinesia ; Fluorescence polarization ; Phenothiazines ; Platelet membranes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phenothiazine administration to psychiatric patients is associated with an increase in the “structural order” of platelet membranes as determined by steady-state fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially in the hydrocarbon region of cell membranes (Zubenko and Cohen 1984, 1985a, b). In this study, platelet membranes prepared from a group of psychiatric patients who developed tardive dyskinesia following chronic treatment with phenothiazines exhibited a significant elevation in DPH fluorescence polarization when compared to similar preparations from an otherwise matched group of patients who had no symptoms or history of tardive dyskinesia. The distribution of polarization values obtained for the tardive dyskinesia group displayed minimal overlap with that of an unmedicated, psychiatrically-healthy control group matched for age and gender. The fluorescence polarization of DPH-labelled platelet membranes was not significantly correlated with phenothiazine daily dose or serum cholesterol concentration in the phenothiazine-treated patient groups, or with dyskinesia severity (AIMS rating) in the tardive dyskinesia group. Patient gender and the presence of an affective disorder did not significantly correlate with DPH fluorescence polarization. The potential physiological and clinical significance of these findings is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00652246
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    Paper (German National Licenses)
    Fulltext
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