2007 Fiscal Year Final Research Report Summary
Effects of antipsychotic drugs on plasma membrane permeability and fluidity in the rat brain as revealed by dynamic positron autoradiography and fluorescence polarization study
| Project/Area Number |
16591127
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | University of Fukui |
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Principal Investigator |
MURATA Tetsuhito University of Fukui, Faculty of Medical Sciences, Associate Professor (80200294)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIBAYASHI Yasuhisa University of Fukui, Biomedical Imaging ResearchCenter, Professor (50165411)
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| Project Period (FY) |
2004 – 2007
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| Keywords | Brain slice / Positron / Neurotoxicitv / Membrane permeabilit / Membrane fluidity / Antinsvchotic drugs / Glucose metabolism |
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| Research Abstract |
Antipsychotic drugs are widely used in the treatment of psychotic disorders, but the use of the drugs is limited by their tendency to induce serious side effects. Although most previous studies compared the cytotoxic effect of antipsychotic drugs on non-neuronal cell types, little is known about the difference among these drugs in the potency to induce neurotoxicity, especially in the potency to interact with the plasma membrane in the central nervous system. Thus, a comparative study was initiated on the potency of the interaction of three antipsychotic drugs, i.e., chlorpromazine (CPZ), haloperidol (HAL) and sulpiride (SUL), with the plasma membrane in the rat brain. CPZ loading 100 μM) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-dipheny1-1,3,5-hexatriene). On the other hand, a higher concentration of HAL (1 mM) was required to observe these effects. However, SUL failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to induce plasma membrane permeabilization and fluidization: CPZ > HAL > SUL. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side effects such as parkinsonism and tardive dyskinesia.
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[Journal Article] Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain2008
Author(s)
Maruoka, N., Murata, T., Omata, N., Takashima, Y., Fuiibavashi. Y, Wada, Y
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Journal Title
J Psychopharmacol 22(2)
Pages: 119-127
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of chlorpromazine on plasma membrane permeability and fluidity in the rat brain : A dynamic positron autoradiography and fluorescence polarization study2007
Author(s)
Maruoka, N., Murata. T., Omata, N., Takashima, Y., Tanii, H., Yonekura, Y., Fuiibavashi, Y., Wada, Y
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Journal Title
Prog Neuropsychopharmacol Biol Psychiatry 31(1)
Pages: 178-186
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of haloperidol and its pyridinium metabolite on plasma membrane permeability and fluidity in the rat brain2007
Author(s)
Murata, T., Maruoka, N., Omata, N., Takashima, Y., Igarashi, K. Kasuya, F., Fuiibavashi. Y., Wada, Y
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Journal Title
Prog Neuropsychopharmacol Biol Psychiatry 31(4)
Pages: 848-857
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain2007
Author(s)
Murata. T., Maruoka, N., Omata, N. ; Takashima, Y., Fuiibavashi, Y., Yonekura, Y., Wada, Y
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Journal Title
Int J Neuropsychopharmacol 10
Pages: 683-689
Description
「研究成果報告書概要(欧文)」より
