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Neurochemical study on pharmachological action of antimanic drugs using by microdialysis method

Research Project

Project/Area Number 02670513
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionYamanashi Medical College

Principal Investigator

TETSUHIKO Kariya  Yamanashi Medical College, Psychiatry, Professor, 医学部, 教授 (60014023)

Co-Investigator(Kenkyū-buntansha) SATO Yoshio  Yamanashi Medical College, Psychiatry, Research Associate, 医学部, 助手 (40215869)
SHIOE Kunihiko  Yamanashi Medical College, Psychiatry, Research Associate, 医学部, 助手 (90215939)
ASADA Takashi  Yamanashi Medical College, Psychiatry, Research Associate, 医学部, 助手 (90184142)
NAKAGAWARA Michio  Yamanashi Medical College, Psychiatry, Professor, 医学部, 講師 (50114773)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsbrain microdialysis / alpha_2 adrenoceptor / MHPG / hyper activity / strain difference / PNMT / microdialysis / Strain difference / α_2 receptor / noradrenergic function / neuropeptide Y / DCMβ / yohimbine
Research Abstract

Two animal experiments and one human study were performed for investigating the mode of action of antimanic drugs.
In a human study, growth hormone(GH)response to desmethylimipramine(DMI)and clonidine was measured in healthy subjects. Of six subjects tested three times at 6-month intervals, five always showed a stable growth hormone response, whereas only one had a rather instable GH response. The blunted GH response to DMI and clonidine was seen in a subject. These results suggested that DMI and clonidine stimulated GH secretion test may be vulnerability markers for central postsynaptic a2 adrenergic function. Those were published in "Seishinigaku".
In animal studies, locomotor activity counts were determined in Fischer 344 rats after a single administration of a phenylethanolamine-N-methyltransferase(PNMT)inhibitor, DCMB. This drug inhibits PNMT as well as az adrenoceptor. Then, yohimbine, pure az adrenoceptor inhibitor, was used as a positive control. In Fischer 344 rats, a2 adrenocep … More tor subsensitivity and higher PNMT activity were found in the hypothalamus and lower brainstem compared with Buffalo rats. These drugs profused hyperactivity in Fischer 344 rats, but DCMB induced hyperactivity was significantly higher than that induced by yohimbine. This result suggested that adrenergic neuron may regulate central alpha_2 adrenoceptor sensitivity. The effect of yohimbine on 3 methoxy 4 hydroxyphenylethylenglycol(MHPG)in extra cellular fluid of hypothalamus was determined by brain dialysis method in Wistar strain rats. MHPG levels were measured by high performance liquid chromatography. MHPG levels were increased after a single intraperitoneal injection of yohimbine. This result suggested that yohimbine may produce presynaptic alpha_2 adrenoceptor inhibition and that MHPG may a biological marker of presynaptic alpha_2 adrenoceptor sensitivity in hypothalamus. These results were reported at the 5th international Congress of Biological Psychiatry, the 20th Congress of Japanese Psychopharmacology and the 12th Congress of Japanese Biological Psychiatry. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 跡部 勝: "3系統のラットの自発運動量におよぼすyohimbineの影響ーPNMT阻害藥投与時と比較してー" 薬物・精神・行動. 10. 227 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 跡部 勝: "3系統のラットの自発運動量におよぼすPNMT阻害薬の影響" 薬物・精神・行動. 10. 540 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 久保田 正春: "Effect of PhenylethanolamineーNーMethyltransferase Inhibitor on Locomotor Activity in Rats" The Japanese Journal of Psychiatry and Neurology. 44. 783 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐藤 佳夫: "同一健康成人におけるdesmethylimipramineおよびclonidine投与による成長ホルモン分泌刺激試験の比較" 精神医学. 33. 1245-1247 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 中河原 通夫: "クロニジンならびにデスメチルイミラミン負荷によるα_2アドレナリン受容体機能の検査法" 脳と精神の医学. 2. 385-387 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐藤 佳夫: "同一健康成人におけるデスメチルイミプラミンテスト及びクロニジンテストの比較" 薬物・精神・行動. 10. 555 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 假屋 哲彦: "リチウム療法の実際" 医歯薬出版株式会社, 311 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atobe M.: "Effect of yohimbine on the locomotor activity in three different strain rats-Compaved with PNMT inhibitor." Japanese Journal of Psychopharmacology. 10. 227 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atobe M.: "Effect of PNMT inhibitor on the locomotor activity in three different strain rats." Japanese Journal of Psychopharmacology. 10. 540 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kubota M.: "Effect of Phenylethanolamine-N-Methyltransferase Inhibitor on Locomotor Activity in Rats." The Japanese Journal of Psychiatry and Neurology. 44. 783 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sato Y.: "Comparison of Desmethylimipramine Test with Clonidine Test in the Same Healthy Subjects." Clinical Psychiatry. 33. 1245-1247 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakagawara M.: "alpha_2 Adrenergic receptor function tests induced by clonidine and desmethylimipramine." Brain Science and Mental Disorders. 2. 385-387 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kariya T.: "The GABA hypothesis of affective disorders." Pharma Medica. 8. 41-45 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Motohashi N.: "Mode of anticonvulsants for affective disorders." Japanese Journal of Clinical Psychiatry. 20. 421-427 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kariya T.: "Monoaminergic function in affective disorders." Japanese Journal of Neuropsychopharmacology. 13. 131-134 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kariya T.: Lithium Treatment in Psychiatry. Medical Dental Pub., 311 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐藤 佳夫: "同一健康成人におけるdesmethy limipramine…およびclonidine投与による成長ホルモン分泌刺激試験の比較" 精神医学. 33. 1245-1247 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中河原 通夫: "クロニジンならびにデスメチルイミプラミン負荷によるα_2アドレナリン受容体機能の検査法" 脳と精神の医学. 2. 385-387 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 中河原 通夫: "神経伝達物質・受容体。" 精神科治療学. 6. 951-958 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 假屋 哲彦: "3 向精神薬" 臨床医. 17. 673-677 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 本橋 伸高: "気分安定薬のある抗けいれん薬の作用機序に関する研究" 神経化学. 30. 128-129 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 本橋 伸行: "感情障害に対する抗けいれん薬の作用機序" 臨床精神医学. 20. 421-427 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 朝田 隆,假屋 哲彦: "うつ病(単極型)とうつ状態" 精神科Mook(精神科領域における薬物療法). 増刊1. 281-291 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kubota,M.,Nakagawara,M.Atobe,M.,Kariya,T.: "Effect of PhenylethanolamineーNーMethyltransferase Inhibitor on Locomotor Activity in Rats." The Japanese of Psychiatry and Neurology. 44. 783 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 跡部 勝、中河原 通夫、久保田 正春、渡辺 ちさと、假屋 哲彦: "3系統のラットの自発運動量におよぼすyohimbineの影響ーPNMT阻害薬投与時と比較してー" 薬物・精神・行動. 10. 227 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 假屋 哲彦: "躁うち病治療薬の基礎と臨床(第20回日本神経精神薬理学会年会、会長講演)" 薬物・精神・行動. 10. 447 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 跡部 勝,中河原 通夫,久保田 正春,清水 ちさと,假屋 哲彦: "3系統のラットの自発運動量におよぼすPNMT阻害薬の影響" 薬物・精神・行動. 10. 540 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakagawara,M.,Sioe,K.,Kariya,T.: "Determination of βーPhenylethylamine in plasma by Capillary gas chromatographyーchemical ionization mass spectrometry." Biogenic Amines.

    • Related Report
      1990 Annual Research Report
  • [Publications] 假屋 哲彦,佐藤 佳夫(分担執筆): "リチウム療法の実際(医歯薬出版)(分担執筆:リチウムによる躁うつ病の予防と維持療法の問題点)(分担執筆163ー184)" 渡辺 昌祐,古川 達雄,江原 嵩,假屋 哲彦(編集), 311 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2017-10-06  

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