臺灣博碩士論文加值系統

右美沙芬 (dextromethorphan) 目前在臨床上主要用途是抑制咳嗽，為一種中樞性止咳劑，其化學結構是右旋性的嗎啡喃且沒有類鴉片之副作用，而且已被應用在止咳至少40年以上；本實驗主要的目的為評估右美沙芬與其代謝物—甲氧基嗎啡喃 (3-methoxymorphinan)與右啡烷 (dextrorphan)是否具有局部麻醉之效用；實驗方法係選擇大白鼠的周邊坐骨神經阻斷模式評估其運動功能 (motor function)、本體感覺(proprioception) 及疼痛反應(nociception)。
目前臨床上最常使用的局部麻醉劑是利多卡因 (lidocaine) ，所以本實驗選擇利多卡因做為實驗對照組。使用右沙美芬及其兩個主要代謝產物右啡烷與甲氧基嗎啡喃，針對藥物效力和藥物所持續時間，以及合併利多卡因一起給予時所產生之效能做評估。實驗結果在藥物效力的排列為：利多卡因＞右美沙芬＞甲氧基嗎啡喃＞右啡烷 (p < 0.01)；藥物持續時間則是甲氧基嗎啡喃與右啡烷藥效持續時間比利多卡因長 (p < 0.05)。當右美沙芬、右啡烷、甲氧基嗎啡喃與利多卡因合併給予具有加成作用 (additive effect) 。因此右美沙芬、右啡烷與甲氧基嗎啡喃在周邊坐骨神經具有局部麻醉效用，無論是運動功能、本體感覺或疼痛反應之藥物效力與持續時間都比利多卡因長；而且當右美沙芬、右啡烷、甲氧基嗎啡喃與利多卡因合併給予在大白鼠周邊的坐骨神經阻斷上亦具有加成作用。
關鍵字：右美沙芬、局部麻醉劑、坐骨神經阻斷。

Dextromethorphan has been used as an antitussive for more than 40 years and is considered a drug with a good margin of safety. The aim of the study was to evaluate whether dextromethorphan and its metabolites (3-methoxymorphinan and dextrorphan) had local anesthetic effect. Using a method of rat sciatic nerve blockade to evaluate the potency and duration of the three drugs.The items of the evaluation were motor function, propioception, and nociception. Lidocaine was used as a control. We found that dextromethorphan and its metabolites produced dose-related local anesthetic effects on sciatic nerve blockade. The potency from the top were lidocaine,dextromethorphan,3-methoxymorphinan, and dextrorphan ( p < 0.01 for each comparison). Under an equi-potent basis, dextrorphan and 3-methoxymorphinan had longer action than that of lidocaine ( p < 0.05 for each comparison). Co-administration of dextromethorphan or its metabolites with lidocaine produced additive effect on sciatic nerve blockade. In conclusion, dextromethorphan and its metabolites (3-methoxymorphinan and dextrorphan) had local anesthetic effect on sciatic nerve blockades of motor function, proprioception and nociception. Their duration of action was longer than that of lidocaine. Co-administration of dextromethorphan and its metabolites produced additive effect on sciatic nerve blockade.

Key words: Dextromethorphan, Local Anesthetic Effect, Sciatic Nerve Blockade.

目錄
摘要 I
Abstract II
誌謝 IV
目錄 V
圖表目錄 VI
縮寫對照表 IX
第1章 前言 1
第2章 文獻回顧 4
2.1 局部麻醉劑 4
2.1.1 局部麻醉劑的歷史 4
2.1.2 局部麻醉劑之藥理作用 4
2.1.3 局部麻醉劑之化學結構 5
2.1.4 局部麻醉劑的藥物動力學 7
2.1.5 局部麻醉劑的副作用與毒性 7
2.2 鹽酸利多卡因 Lidocaine Hydrochloride 之介紹 8
2.2.1 利多卡因 (lidocaine) 之物化性質 8
2.2.2 利多卡因之藥理學 9
2.2.3 利多卡因之藥物動力學 9
2.2.4 利多卡因之副作用與毒性 9
2.2.5 利多卡因臨床上之使用 10
2.2.6 利多卡因與藥品之交互作用 10
2.3 右美沙芬Dextromethorphan 之介紹 10
2.3.1 右美沙芬之物化性質 11
2.3.2 右美沙芬之藥理學 12
2.3.3 右美沙芬之藥物動力學 12
第3章 研究材料與方法 14
3.1 研究材料 14
3.1.1 實驗動物 14
3.1.2 實驗藥品 14
3.1.3 實驗相關儀器及材料 15
3.2 研究方法 15
3.2.1 動物實驗前準備 15
3.2.2 藥物注射 15
3.2.3 藥物配製 16
3.2.4 實驗流程 16
3.2.5 神經行為學的評估 17
3.2.6 實驗結果的分析流程 18
3.2.7 50％最大有效反應劑量 (ED50) 19
3.2.8 統計方法 19
第4章 結 果 20
4.1 右美沙芬與利多卡因之坐骨神經阻斷效能 20
4.2 右美沙芬、右啡烷、甲氧基嗎啡喃與利多卡因藥效劑量反應 20
4.3 右美沙芬、右啡烷、甲氧基嗎啡喃和利多卡因藥物效力之維持時間 21
4.4 右美沙芬、右啡烷或甲氧基嗎啡喃有/無合併利多卡因在大白鼠周邊坐骨神經的影響 21
第5章 討 論 42
第6章 結 論 45
參考文獻 46
摘要 I
Abstract II
誌謝 IV
目錄 V
圖表目錄 VI
縮寫對照表 IX
第1章 前言 1
第2章 文獻回顧 4
2.1 局部麻醉劑 4
2.1.1 局部麻醉劑的歷史 4
2.1.2 局部麻醉劑之藥理作用 4
2.1.3 局部麻醉劑之化學結構 5
2.1.4 局部麻醉劑的藥物動力學 7
2.1.5 局部麻醉劑的副作用與毒性 7
2.2 鹽酸利多卡因 Lidocaine Hydrochloride 之介紹 8
2.2.1 利多卡因 (lidocaine) 之物化性質 8
2.2.2 利多卡因之藥理學 9
2.2.3 利多卡因之藥物動力學 9
2.2.4 利多卡因之副作用與毒性 9
2.2.5 利多卡因臨床上之使用 10
2.2.6 利多卡因與藥品之交互作用 10
2.3 右美沙芬Dextromethorphan 之介紹 10
2.3.1 右美沙芬之物化性質 11
2.3.2 右美沙芬之藥理學 12
2.3.3 右美沙芬之藥物動力學 12
第3章 研究材料與方法 14
3.1 研究材料 14
3.1.1 實驗動物 14
3.1.2 實驗藥品 14
3.1.3 實驗相關儀器及材料 15
3.2 研究方法 15
3.2.1 動物實驗前準備 15
3.2.2 藥物注射 15
3.2.3 藥物配製 16
3.2.4 實驗流程 16
3.2.5 神經行為學的評估 17
3.2.6 實驗結果的分析流程 18
3.2.7 50％最大有效反應劑量 (ED50) 19
3.2.8 統計方法 19
第4章 結 果 20
4.1 右美沙芬與利多卡因之坐骨神經阻斷效能 20
4.2 右美沙芬、右啡烷、甲氧基嗎啡喃與利多卡因藥效劑量反應 20
4.3 右美沙芬、右啡烷、甲氧基嗎啡喃和利多卡因藥物效力之維持時間 21
4.4 右美沙芬、右啡烷或甲氧基嗎啡喃有/無合併利多卡因在大白鼠周邊坐骨神經的影響 21
第5章 討 論 42
第6章 結 論 45
參考文獻 46
作者簡介 53

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