表現強效鎮痛作用並減少副作用之新型鴉片受體促效劑

Taipei Medical University Institutional Repository > 醫學科技學院 > 神經再生醫學博士學位學程 > 博碩士論文 > Item 987654321/64743

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題名:	表現強效鎮痛作用並減少副作用之新型鴉片受體促效劑 Novel Opioid Receptors Agonists Presented Robust Analgesic Effect with Reduced Side Effects
作者:	徐瑛婷 Hsu, Ying-Ting
貢獻者:	神經再生醫學博士學位學程莊健盈葉修華
關鍵詞:	鴉片類藥物;陣痛效果;副作用 Opiods;Analgesic Effects;Side Effects
日期:	2024-01-17
上傳時間:	2024-11-26 15:59:58 (UTC+8)
摘要:	數百年以來，鴉片類藥物一直被廣泛應用於全球各地，作為應對各種不同疼痛的臨床指引。然而，這些藥物仍然對使用者產生諸多困擾。最主要的原因在於它們不可忽視且多樣的副作用，以及由此引發的藥物濫用等問題。止痛效果和副作用的產生涉及到鴉片類藥物和鴉片受體之間複雜的交互作用。如何讓這類藥物保持強效的止痛能力，同時減少對人們的不良影響，是近年來科學家們正努力嘗試解決的問題。在這項研究中，我們首先針對一系列經過結構修改的化合物進行了體外實驗，觀察這些化合物與不同的鴉片受體之間的互動狀態。基於這些細胞層面的實驗結果，我們初步評估並挑選了一些具有影響神經信號傳遞能力的化合物，亦即作為優秀的鴉片受體促效劑所需的特性。隨後，我們將挑選的化合物推進到動物體內進行測試。在不同疼痛模型的動物實驗中，我們確認這些化合物能夠以比嗎啡低許多的劑量產生明顯的止痛效果。不僅如此，在測試了多種不同的副作用後，結果顯示幾乎所有副作用都有顯著的減少。除此之外，我們在實驗中也使用了不同基因型的小鼠，為這些化合物的止痛效果、副作用以及它們與鴉片受體之間的關聯，提供了更多的線索。總結而言，這些經結構修改的鴉片類藥物，藉由不同層面的研究和測試，其中部分化合物確實展現了傑出的止痛效果，同時減少了擾人的副作用。這項研究成果有望為優化鴉片類藥物的相關研究提供具價值性的參考依據。 For centuries, opioid medications have been widely utilized globally as a clinical guideline for addressing various forms of pain. However, these drugs continue to pose numerous challenges for users. The primary concern stems from their undeniable and diverse side effects, as well as the resultant issues of drug abuse. The genesis of analgesic effects and side effects involves a complex interaction between opioid drugs and opioid receptors. The challenge faced by scientists in recent years is how to maintain the potent analgesic capabilities of these drugs while concurrently minimizing adverse effects on individuals. In this research endeavor, we initiated by in vitro experiments focusing on a series of structurally modified compounds. These experiments aimed to observe the interaction states between these compounds and various opioid receptors. Based on the results at the cellular level, we conducted a preliminary assessment and selected compounds demonstrating the capacity to influence neural signal transmission, which is the qualities requisite for excellent opioid receptor agonists. Subsequently, we progressed to in vivo testing of the chosen compounds in animal subjects. Across diverse animal experiments simulating different pain models, we affirmed that these compounds could elicit significant analgesic effects at substantially lower doses than morphine. Furthermore, upon testing various side effects, the results indicated a notable reduction in almost all adverse reactions. Additionally, we incorporated mice with different genotypes in our experiments, providing further insights into the analgesic effects of these compounds, their side effects, and their associations with opioid receptors. In summary, these structurally modified opioid medications, subjected to multifaceted research and testing, demonstrated outstanding analgesic effects while concurrently reducing disruptive side effects. The outcomes of this study hold promise in furnishing valuable reference points for optimizing research related to opioid medications.
描述:	博士指導教授：莊健盈共同指導教授：葉修華口試委員：劉景平口試委員：高祖仁口試委員：葉修華口試委員：莊健盈口試委員：林惠菁
附註:	論文公開日期：2024-02-02
資料類型:	thesis
顯示於類別:	[神經再生醫學博士學位學程] 博碩士論文

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