2004 Fiscal Year Final Research Report Summary
Mechanism of metabolic activation of xenobiotics in brain
| Project/Area Number |
14572116
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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 |
Environmental pharmacy
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
KASUYA Fumiyo Kobe-gakuin University, Faculty of Pharmaceutical Sciences, 薬学部, 講師 (80131522)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Haloperidol / Hemoprotein / Peroxides / Neuronaltoxicity / Brain / Accumulation / 脳内蓄積性 |
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| Research Abstract |
Haloperidol is a clinically useful antipsychotic drug, but it has severe extrapyramidal side-effects. HPP^+, the active metabolite of haloperidol, may be involved in the development of drug-induced parkinsonism with chronic HP therapy. HPP^+ was formed by P-450 CYP3A4 in liver. HPP^+ found in rat brain following administration of HP may be formed peripherally and then be transported through the blood-brain barrier. However, HPP^+ in brain was also found to be formed by non-P450 hemoproteins in the presence of the peroxides. Further, HPP^+ was producted not by the nonheme metal ions but by metalloporphyrine in combination with the peroxides. Increase of lipid peroxide levels in rat brain with years of rat resulted in increasing generation of HPP^+ in rat brain homogenates. These findings suggest that formation of HPP+ from HP in human brain may increase with increasing age and it may be easy to cause Parkinson's disease in old age.
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