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

出现发热、肌阵挛、多汗和精神状态改变等临床症状的马林碱被认为是一种严重的不良反应。近年来，抗抑郁药诱导的马林氏综合征也有报道。本研究的目的是制备马林氏综合征大鼠模型，用几种5-羟色胺(5-羟色胺)再摄取抑制剂诱导马林氏综合征的病因性症状之一发热，以阐明抗抑郁药的药代动力学与脑内5-羟色胺水平或发热的关系。1997年，首先，我们建立了测定生物样品中抗抑郁剂氯丙咪嗪的高效液相色谱方法。用分析方法测定正常大鼠静脉注射氯丙咪嗪后的血药浓度和脑内药物浓度，并对其药代动力学进行分析。在PO/AA区注射神经递质释放剂藜芦碱后，大鼠腹腔注射氯丙咪嗪，复制高热模型，作为马林证的标志物。1998年，我们测定了联合应用藜芦碱和氯丙咪嗪后肥胖脑中5-羟色胺的水平。服用藜芦碱的大鼠脑内5-羟色胺水平明显高于未服用藜芦碱的大鼠。

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.