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Analysis of the relationship between antidepressant-induced Syndrome maline and Pharmaco Kinetic

Research Project

Project/Area Number 09672320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionThe University of Tokyo

Principal Investigator

OHTANI Hisakazu  Fac.of Med.Univ.of Tokyo, assistant, 医学部・附属病院, 助手 (70262029)

Co-Investigator(Kenkyū-buntansha) KOTAKI Hajime  Inst.of Med.Sci., Univ.of Tokyo, Director of Pharmacy, 医科学研究所・附属病院, 薬剤部長
AOYAMA Takao  Fac.of Med.Univ.of Tokyo, assistant, 医学部・附属病院, 助手 (60262028)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsSyndrome maline / antidepressant / Clomipramine / Veratrine / fever / 5-HT / microdialysis / rats / 発熱反応
Research Abstract

Syndrome maline with clinical futures such as fever, myoclonus, hidropoiesis and mental status changes is recognized as a severe adverse reaction. Recently, the syndrome maline induced by antidepressant has been also reported in human beings.
The purpose of the present study is to prepare the syndrome maline model rats, to induce fever which is one of pathognomonic symptom of the syndrome maline after administration of several serotonin (5-HT) reuptake inhibitors to the model rats, to elucidate the relationship between pharmacokinetics of antidepressant and 5-HT levels in brain, or elevated fever. Final goal is In addition.
In 1997, Firstly, we developed a high performance liquid chromatographic method for determination of antidepressant, clomipramine, in biological samples. Clomipramine concentrations in plasma and brain after intravenous administration of the drug to intact rats were measured by the analytical method, and the pharmacokinetics of clomipramine was analyzed. Then, clomipramine was administered intraperitoneally to rats after veratrine, a neurotransmitter releasing agent, was injected to the PO/AH.By the administration method, we could reproduced the elevated fever as a marker of the syndrome maline. In 1998, we measured 5-HT level in fat brain after coadministration of veratrine and clomipramine. The 5-HT level in brain with veratrine we higher than that without.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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