以神經傳導物質及其代謝物含量的變化探討選擇性血清素再回收抑制劑應用於減輕嗎啡戒斷反應及其藥效機轉

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Title:	以神經傳導物質及其代謝物含量的變化探討選擇性血清素再回收抑制劑應用於減輕嗎啡戒斷反應及其藥效機轉 Study on the Efficacy and Mechanism of Selective Serotonin Reuptake Inhibitors in Reducing Morphine-Withdrawal Symptoms by the Changes of Neurotransmitter and Metabolite Levels
Authors:	劉國盛宋國峻王志中
Contributors:	藥物科技研究所
Keywords:	選擇性血清素再回收抑制劑嗎啡戒斷現象微透析 selective serotonin reuptake inhibitors morphine withdrawal microdialysis
Date:	2010
Issue Date:	2011-12-22 09:47:25 (UTC+8)
Abstract:	類嗎啡類(opioids)成癮之療法，目前皆著重於以單一類嗎啡藥物來進行治療，然而影響其成癮之因素很多，其中精神因素即佔了重要的一部份，因此若能以治療精神疾病之藥物如選擇性血清素再回收抑制劑(selective serotonin reuptake inhibitors; SSRIs)來作為治療之藥物，將有可能加強減輕其戒斷症狀，提供另一治療之新選擇。在本研究中我們探討以SSRIs應用於減輕嗎啡戒斷反應及其藥效機轉。本研究共分成二年：第一年建立以微透析高效能液相層析法，分析腦中指標神經傳導物質及其代謝物之變化，確認其與減輕嗎啡戒斷反應之相關性及其動物模式。第二年探討SSRIs對於具有嗎啡身體依賴性動物在戒斷上之療效(single use)。本研究順利開發一個簡單高效能液相層析-電化學偵測器之方法可同時偵測單胺類神經傳導物質及其代謝物，其最低偵測極限範圍為0.3-127nM，線性迴歸曲線之r2在0.99以上，而利用此分析方法結合微透析技術，觀察大鼠在嗎啡注射下腦部之紋狀體核區神經傳遞物質及其代謝物濃度之變化情形。在給予不同之SSRIs時，其神經傳導物質及其代謝物之變化，各有所不同，然而目前則以sertraline所造成之含量變化和嗎啡較為類似，能有效增加各種神經傳導物質及其代謝物之含量，為較有潛力成為治療類嗎啡類成癮之藥物。 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 an important role. If selective serotonin reuptake inhibitors (SSRIs, a psychosis drug) are applied for an treatment, the withdrawal symptoms can be reduced and is another option to treat opioid dependence . In this study, the efficacy and mechanism of SSRIs in reducing morphine-withdrawal symptoms were investigated. The study takes 2 years. In the first year, an animal model and the target neurotransmitter and metabolite levels in brain were set up by using microdialysis coupled with HPLC-ECD to evaluate the efficacy of SSRIs. In the second year, an estimative model was set up to discover the drugs. A Simple high-performance liquid chromatography with electrochemical detection using microdialysis was developed for simultaneous determination of monoamine neurotransmitters and metabolite levels in the rat corpus striatum. The detection limits of these compounds were 0.3-127nM, the correlation coefficients of regression were more than 0.99. The method has been successfully applied to measure the neurotransmitters and their metabolite levels in the rat corpus striatum by morphine injection. Each SSRI has different effects of neurotransmitter and metabolite levels in brain. But the effects of sertraline are more like to morphine, it can efficiently enhance the levels of neurotransmitters and their metabolite. Sertraline may be a candidate drug to treat opioid dependence.
Relation:	計畫編號：NSC98-2314-B041-001-MY2 計畫年度：99；起迄日期：2010-08-01~2011-07-31 核定金額：1,020,000
Appears in Collections:	[Dept. of Pharmacy] MOST Project

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