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

临床表现为发热、肌阵挛、出汗和精神状态改变的综合征被认为是严重的不良反应。近年来，抗抑郁药引起的抑郁综合征在人类也有报道，本研究旨在制备抑郁综合征大鼠模型，并通过给药5-羟色胺（5-HT）再摄取抑制剂，诱发抑郁综合征的特征性症状之一发热，探讨抗抑郁药的药代动力学与脑内5-HT水平的关系，或者高烧另外，1997年，我们首先建立了生物样品中抗抑郁药氯丙咪嗪的高效液相色谱测定方法。用分析方法测定了氯丙咪嗪在大鼠体内的血药浓度和脑组织浓度，并对氯丙咪嗪的药代动力学进行了分析。然后，在PO/AH注射神经递质释放剂藜芦碱后，腹腔注射氯丙咪嗪，通过给药方法，我们可以复制高热作为综合征的标志。1998年，我们测定了藜芦碱和氯丙咪嗪联合给药后脂肪脑中5-HT的含量。藜芦碱组脑内5-HT含量明显高于对照组。

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.