| 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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,050,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Brain slice / Positron / Neurotoxicitv / Membrane permeabilit / Membrane fluidity / Antinsvchotic drugs / Glucose metabolism / 耐糖能異常 / ポジトロン標識化合物 / 脳機能イメージング / 膜透過性 / 膜流動性 / 解糖系 |
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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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