Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/2581
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    標題: 探討以三環抗憂鬱藥應用於減輕嗎啡戒斷反應及藥效機轉探討(新制多年期第1年)
    作者: 劉國盛
    宋國峻
    王志中
    貢獻者: 藥物科技研究所
    日期: 2007
    上傳時間: 2008-07-31 16:51:16 (UTC+8)
    出版者: 台南縣:嘉南藥理科技大學藥物科技研究所
    摘要: 前對於類鴉片類(opioids)成癮之療法,皆著重於以單一類鴉片(opioid)藥物來治療類鴉片成癮。然而類鴉片之成癮因素很多,精神因素也是其中重要之一環,因此若能以治療精神病用之藥物如三環抗憂鬱藥(tricyclic antidepressants, TCAs)來做為輔助療法之藥物,將有可能加強原本藥物之療效並減輕其戒斷症狀。在我們先期研究証實三環抗憂鬱藥中之 amitriptyline 具有降低小鼠之戒斷反應,在本研究中我們擬擴大研究,探討以三環抗憂鬱藥應用於減輕嗎啡戒斷反應及藥效機轉探討,因此我們將以小鼠為研究對象,廣泛性探討三環抗憂鬱藥對於誘發嗎啡身體依賴性 (physical dependence)動物之療效,並探討其和buprenorphine 共同給藥時之作用情形,並深入進行分子機轉上之探討。本研究共分三年:第一年建立相關動物模式,廣泛性地探討三環抗憂鬱藥對於誘發嗎啡身體依賴性動物在戒斷上之療效(single use),找出最佳之三個藥物,並作出劑量反應之相關性。第二年將利用isobologram 方法,探討此三個藥物分別和buprenorphine 共同使用之療效(combination)。第三年將建立小鼠脊髓的蛋白質分析方法,探討三環抗憂鬱藥單一使用及和buprenorphine 合併使用,對於誘發嗎啡身體依賴性動物之脊髓的蛋白質變化情形。
    The treatments of opioid addiction focus on the single use of opioids presently. However, there are many opioid addiction-associated factors, among which a psychological factor plays a significant role. If tricyclic antidepressants (TCAs, a psychosis drug) are applied for an auxiliary treatment, the effect of the main medicine can be enhanced and the withdrawal symptoms reduced. In our preceding study, amitriptyline (a TCA) reduces the withdrawal symptoms in mice. In this study, the efficacy and mechanism of TCAs in reducing morphine-withdrawal symptoms will be further investigated, besides extensively evaluating the effect of: TCAs on morphine physical dependence in mice; the combination of TCAs and buprenorphine; TCAs on molecular mechanism. The study takes 3 years. In the first year, an animal model is set up to discover the three most effective drugs and the association among their dose-response curves, by extensively evaluating the efficacy of TCAs single use on morphine physical dependence. In the second year, the isobologramic methodology for the interaction between these drugs and buprenorphine is studied. In the third year, the proteomic analysis is founded for the spinal protein expression in the single use of TCAs and the combination of buprenorphine in mice.
    關聯: 計畫編號:NSC96-2314-B041-002-MY2
    顯示於類別:[藥學系(所)] 科技部計畫

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