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Psychoactive substances metabolism and cytotoxicity in the brain and liver

Research Project

Project/Area Number 12670959
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionAzabu University

Principal Investigator

IWAHASHI Kazuhiko  Azabu university, College of Environmental Health, Professor, 環境保健学部, 教授 (00232695)

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)
中村 和彦  麻布大学, 環境保健学部, 講師 (80263911)
伊藤 正裕  香川医科大学, 医学部, 助教授 (00232471)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
KeywordsPsycoactive substance / CYP2A6 / CYP1A2 / 薬物の副作用 / 向精神薬 / P450 / 副作用 / CYP2A6 / CCK / CYP / 精神作用物質 / 細胞障害
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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Yoshihara E: "The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patients"Neuropsychobiology. 41. 124-126 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshihara E: "The effects of the ALDH2^*1/2, CYP2E1 C1/C2 and C/D genotypes on blood ethanol elimination"Drug and Chemical Toxicology. 23. 371-379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y: "Isolation of Borna disease virus from human brain tissue"J. Virol.. 74. 4601-4611 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwahashi K: "Analysis of the metabolism of haloperidol (HP) and its neurotoxic pyridinium metabolite(HPP^+)in patients with drug-induced parkinsonism"Clin Chim Acta. 298. 193-195 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K.: "Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase : clinical features of alcoholics with ALDH 2^*2"Addiction Biology. 5. 307-311 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwahashi K: "Analysis of the metabolism of haloperidol (HP) and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism"Neuropsychobiology. 44. 126-128 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zang X.: "Lack of association between smoking and CYP2A6 gene polymorphism in a Japanese population"Jpn J Alcohol & Drug Dependence. 36. 486-490 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue M.: "Change of Bcl-2 and bax mRNA expressions in the ethanol-treated mouse brain"Jpn J Alcohol & Drug Dependence. 37. 120-129 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zang X.: "Effects of whole delection of CYP2A6 on nicotine metabolism in humans"Drug and Chemical Toxicology. 25. 203-213 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K.: "Peripheral-type benzodiazepine receptors on platelets are correlated with the degrees of anxiety in normal human subjects"Psychopharmacology. 162. 301-303 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 岩橋和彦: "遺伝子から心を見る、現代のエスプリ"至文堂. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 岩橋和彦: "「酵素活性」から心を見る、現代のエスプリ"至文堂. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshihara E.: "The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patients"Neuropsychobiology. 41. 124-126 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshihara E.: "The effects of the ALDH2*1/2, CYOP2E1 C1/C2 and C/D genotypes on blood ethanol elimination"Drug and Chemical Toxicology. 23. 371-379 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura Y.: "Isolation of Borna disease virus from human brain tissue"J. Virol.. 74. 4601-4611 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwahasi K.: "Analysis of the metabolism of haloperidol (HP) and its neurotoxic pyridinium metabolite (HPP^+) in patients with drug-induced parkinsonism"Clin Chim Acta. 298. 193-195 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K.: "Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase: clinical features of alcoholics with ALDH 2*2"Addiction Biology. 5. 307-311 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwahashi K.: "Analysis of the metabolism of haloperidol (HP) and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism"Neuropsychobiology. 44. 126-128 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zang X.: "Lack of association between smoking and CYP2A6 gene polymorphusm in Japanese population"Jpn J Alcohol & Drug Dependence. 36. 486-490 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue M., Nakamura K., Iwahashi K., Ameno K., Itoh M.,Suwaki H.: "Change of Bcl-2 and bax mRNA expressions in the ethanol-treated mouse brain"Jpn J Alcohol & Drug Dependence. 37. 120-129 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zang X.: "Effects of whole delection of CYP2A6 on nicotine metabolism in humans"Drug and Chemical Toxicology. 25. 203-213 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K.: "Peripheral-type benzodiazepine receptors on platelets are correlated with the degrees of anxiety in normal human subjects"Psychopharmacology. 162. 301-303 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K., Fukunishi I., Nakamoto I., Iwahashi K., Yoshii M.: "Peripheral-type benzodiazepine receptors on platelets are correlate with the decrease of anxiety in normal human subjects"Psychopharmacology. 162. 301-303 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zang X., Ameno K., Iwahashi K.et al.: "Effects of whole delection of CYP2A6 on nicotine metabolism in humans"Drug and Chemical Toxicology. 25. 203-213 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwahashi K., Ameno K., Nakamura K.: "Analysis of the metabolism of HP and its neurotoxic pyridium metabolite in patients with drug-induced parkinsonisms"Neuropsychobiology. 44. 126-128 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwahashi K. et al.: "Analysis of the metabolism of haloperidol and its neurotoxic pyridinium metabolite in patients with drug-induced par kinsonism"Neuropsychobiology. 44. 126-128 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩橋 和彦: "ニコチン(タバコ)依存とCCKおよびCYP2A6に関する分子生物学的研究"臨床精神医学. 31(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩橋和彦,飴野清,中村和彦 他: "薬剤性パーキンソンニズムおよび心毒性の発症機序の解析-ハロペリドール血中濃度とCYP2D6の遺伝子多型との関連-"脳と精神の医学. 11. 63-66 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwahash K,Nmeno K,Nakamak K, et al: "Analysis of the metabolism of haloperidol (HP) and its neurotoxic pyridinium metabolite (HPPT)in Patients with drug-induced Parkinsonism."Clin Chim Acta. 298. 193-195 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamara K,Iwahashi K,Ito M. et al.: "Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase.clinical features of alcoholics with ALDH*2"Adiction Biology. 5. 307-311 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshihara E,Ameno K.Nakamara K. et al: "The effects of the ALDH2*1/2 CYP2El C1/C2 and C/D genotypes on blood ethunol elimination"Drug and Chemical Toxicology. 23. 371-379 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshihara E.,Nakamara K,Ito M. et al.: "The human serotonin receptor gene(HTR2)Msp1 polymorphism in Japanese schizophrenic and alcoholic patients."Neuropsychobiology. 41. 124-126 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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