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Dopamine D-1, D-2 and Serotonin 2 receptor Occupation by Atypical Antipsychotic Drugs In Vivo.

Research Project

Project/Area Number 02670507
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionHokkaido University

Principal Investigator

MATSUBARA Shigehiro  Hokkaido University School of Medicine Instructor, 医学部, 助手 (40142731)

Co-Investigator(Kenkyū-buntansha) ODAGAKI Yuji  Hokkaido University School of Medicine Instructor, 医学部附属病院, 助手 (10221160)
KOYAMA Tsukasa  Hokkaido University School of Medicine Associate Professor, 医学部, 助教授 (10113557)
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: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsDopamine D-1 receptor / Dopamine D-2 receptor / Serotonin2 receptor / Atypical antipsychotic drugs / EEDQ / In vivo receptor occupancy / 非定型抗精神病薬 / 錐体外路症状 / ジ-パミン受容体 / セロトニン_2受容体 / In vivo受容体占有率
Research Abstract

In vivo occupation of dopamine D-1, D-2and serotonin(5-HT)2 receptors by typical and atypical antipsychotic drugs(APDs)was examined using Nethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline(EEDQ), a protein alkylating reagent which nonselectively and irreversibly inactivates these receptor binding sites. APDs were classified into typical or atypical based on their capacity to induce extrapyramidal side effect(EPS)in man and/or catalepsy in laboratory rodents. Pretreatment of rats with five different classes of typical APDs(haloperidol, 0.25-3 m, /kg ; chlorpromazine, 5-10 mg/k-g ; cisflupenthixol, I mc, /k-g ; zoiepine, 5 mg/kg and nemonapride, 0.5-2 mg/kg potently reversed the EEDQ(8 mg/kg)-induced D-2 receptor inactivation in rat striatum. In contrast, some atypical APDs or its candidates(clozapine, 530 mg/kg ; fluperlapine, 10 mg/ka- risperidone, 0.25 - 3 mg/kg ; setoperone, 0.025 - 0.25 mg/kg ; an-d ORG 5222, 0.25 mg/kg)showed considerable occupation of 5-HT2 receptors in cerebral cortex with smaller or negligible occupation of D-2 and D-1 receptors in striatum. Pretreatment with the other atypical APDs(sulpiride, 30 mgfk-, ; and amperozide, I mg/kg)had no effect on the EEDQ-induced inactivation of these three receptors, although high dose of sulpiride(60 mglkg)and amperozide(5 mg/kg)exhibited slight but significant reversal of D-2 and 5-HT2 receptor inactivation, respectively. It was concluded that a certain group of atypical APDs is characterized by high occupancy of 5-HT2 receptor with lower or minimal occupancy of D-2 and DI receptors in vivo. These pharmacological characteristics of atypical APDs may be relevant in their low capacity to induce EPS and the reported benefical effect on negative symptoms of schizophrenia.

Report

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

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 松原 良次: "非定型抗精神病薬の薬理学的特性に関する研究 ーin vivoにおける脳内dopamine,serotonin受容体占有率の同時測定ー." 精神薬療基金研究年報. 22集. 187-193 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松原 繁広: "定型および非定型抗精神病薬の抗ド-パミンD1、D2、抗セロトニン5ーHT2作用." 精神医学. 33. 117-123 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松原 良次: "非定型抗精神病薬によるラット脳内dopamine,serotonin受容体のin vivoにおける占有率." 神経精神薬理. 14. 145-153 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S.Matsubara: "Dopamine D-1,D-2 and Serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] R. Matsubara: "A study on the Pharmacological Properties of Atypical Antipsychotic Drugs : Dopamine and Serotonin Receptor Occupancy by Antipsychotic Drugs in vivo." Annual Report of the Pharmacopsychiatry Research Foundation.22. 187-193 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Matsubara: "Antidopamine D-1, D-2 and Serotonin 2 Effect of Typical and Atypical Antipsychotic Drugs." Clinical Psychiatry.33. 117-123 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] R. Matsubara: "Dopamine and Serotonin Receptor Occupancy by Atypical Antipsychotic Drugs in vivo." Jpn. J. Neuropsychopharmacol.14. 145-153 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Matsubara: "4. Dopamine D-1, D-2 and Serotonin 2 Receptor Occupation by Typical and Atypical Antipsychotic Drugs in vivo."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松原 良次: "非定型抗精神病薬の薬理学的特性に関する研究ーin vivoにおける脳内dopamine,serotonin受容体占有率の同時測定ー." 精神薬療基金研究年報. 22集. 187-193 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松原 繁広: "定型および非定型抗精神病薬の抗ド-パミンD1、D2、抗セロトニン5ーHT2作用." 精神医学. 33. 117-123 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松原 良次: "非定型抗精神病薬によるラット脳内dopamine,serotonin受容体のin vivoにおける占有率." 神経精神薬理. 14. 145-153 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松原 繁廣: "定型および非定型抗精神病薬の抗ド-パミンD_1,D_2,抗セロトニン5HT_2作用" 精神医学. 33. 117-123 (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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