2002 Fiscal Year Final Research Report Summary
Psychoactive substances metabolism and cytotoxicity in the brain and liver
| Project/Area Number |
12670959
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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 | Azabu University |
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Principal Investigator |
IWAHASHI Kazuhiko Azabu university, College of Environmental Health, Professor, 環境保健学部, 教授 (00232695)
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| Co-Investigator(Kenkyū-buntansha) |
AMENO Kiyoshi Kagawa medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50019626)
YOSHIHARA Eiji Azabu university, College of Environmental Health, Associate Professor, 環境保健学部, 助教授 (80147975)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Psycoactive substance / CYP2A6 / CYP1A2 / 薬物の副作用 / 向精神薬 |
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| Research Abstract |
The relationship between psychoactive substances metabokism by CYPs and the side effects were investigated in nicotine dependents and psychiatric patients treated with psychotropic drugs.
1) The relationship between nicotine metabolism of CYP2A6 and the smoking behavior in Japanese was investigated. There was a significant difference in the frequency of the CYP2A6*4C allele between current smoking group and non-smoking group. The frequency of the CYP2A6*4C allele was higfer in non-smokers than in current smokers. In this study it was suggested that CYP2A6*4C allele which is a whole deleted allele for the human CYP2A6 gene, may prevent the carrier from smoking behavior, while CYP2A6*1A and and CYP2A6*1B allele may play a role to metabolize nicotine to cotinine incurrent smokers.
2) These results in this study suggested that the higher blood olanzapine concentration may be effected by the abnormal metabolism by CYP1A2 and/or CYP2A6, but not always caused hyper glycemia. These supported the idea that not only olanzapine but also an inter mediated metabolite from olanzapine may impair pancreatic beta-cell function, the blood glucose management factor such as beta(3)-adrenergic receptor (beta3AR) and the regulation system of appetite such as the 5-hydroxytryptamine 2C receptor.
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