小瀧 一 東京大学, 医科学研究所・附属病院, 薬剤部長 (50143483)
AOYAMA Takao Fac.of Med.Univ.of Tokyo, assistant, 医学部・附属病院, 助手 (60262028)
KOTAKI Hajime Inst.of Med.Sci., Univ.of Tokyo, Director of Pharmacy
|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)
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.