2020-01-022024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657131摘要：近年來，國際上新興影響精神物質(NPS)的發展趨勢已日趨嚴重，NPS即國內所謂的新興毒品，將已知濫用藥物的化學結構經由變異而來，對其進行較小的結構改造，藉以逃避管制法規的限制，但這些物質仍具有相同的濫用潛力並對人體產生精神危害。這些新興影響精神物質因尚未進行實驗測試，其毒性、成癮性與濫用性在未知的情況下，監管機構難以管理，從而構成了灰色地帶，成為現有法規中的漏洞。目前國內主管機關的資料庫仍無法判別這些新興影響精神物質是否需要被列管，造成管理上的阻礙。若需要等每一項新興影響精神物質進行合成與測試取得實驗數據後才進行評估管制，恐已對社會造成了不可挽回的傷害。如果可以透過電腦模擬技術，自動識別出這些新興影響精神物質的生理作用，可提供國內監管單位作為列管決策的參考，及早向民眾發布相關的警告。電腦模擬篩選技術已被廣泛應用於新藥開發的篩選，但在台灣尚未應用於識別潛在的管制藥品上。因此，為幫助國內監管機構可更好地維護國人健康與安全，本計畫擬建構一套國內完整的管制藥品資料庫，並評估和設計合成卡西酮類新興影響精神物質電腦模擬篩選系統。資料庫將包括所有自2019年起國內的所有管制藥品，並分析和儲存其結構特徵參數與藥毒理等資訊。另以卡西酮的結構為基準，蒐集各國(預計包括來自美國、日本、中國、香港、韓國與新加坡等地)的管制藥品中具有卡西酮相似核心結構的合成卡西酮類化合物，分析其結構特徵，包括藥效基團、結構指紋，原子間距離與構型等參數，這些數據將用於評估與設計電腦模擬篩選系統。該計畫建構的資料庫與電腦模擬篩選系統之設計，將有助於未來作為實際建構合成卡西酮類或其它濫用毒品電腦模擬篩選系統之基礎，達成政府對新興毒品防範未然的對策，有效減少新興影響精神物質之危害。<br> Abstract: In recent years, there is a dangerous emerging trend with regards to new psychoactive substances (NPS): most NPS are structural variants of known substances of abuse, which has undergone minor structural modification to avoid regulation, but these substances have the same potential for abuse and exert similar adverse effects on the human body. These NPS have not been tested in experiments, and their toxicological potential are not fully understood by regulatory agencies, constituting a “gray area” and a loophole in existing regulation. Their addiction or dependency potential are also unknown, making it difficult to manage risks. Existing domestic regulatory database for controlled substances cannot determine whether these NPS should be considered and therefore regulated as substances of abuse. The agency is concerned that if all NPS need to be synthesized and tested to generate substantial experimental data, these substances would have already caused irrevertible harm to our society and implementing regulation only then would be too late. Therefore, if the physiological effects of these structural variants of NPS can be computationally identified, it will be an invaluable reference to our domestic regulatory agency to make informed regulatory decisions. In this way, the agency will be able to issue relevant warnings to the public before it is too late.Computational methods have widely been applied to screening of drug compounds, however it has not been utilized to identify potential substances of abuse for regulatory decisions in Taiwan, to our knowledge. Therefore, to aid in our agency’s effort to better safeguard public health and safety, this project proposes to construct a database for controlled substances and to evaluate and design a computer simulation screening system for synthetic cathinones NPS. The database will be constructed to include all controlled substances known as of 2019, including their structural information, toxicity, physiological effects etc. Next, cathinone-based structures or more boardly referred to as “synthetic cathinones” having similar core structures will be examined closely: including but not limited to their pharmacophore groups, molecular fingerprint, distance between the atoms, configuration etc. These curated databases will include substances of abuse from the United States, Japan, China, Hong Kong, South Korea, Singapore, etc.In summary, the construction of a database and the design of a computer simulation screening system will serve as the foundation to help screen for synthetic cathinones or other drugs of abuse, to achieve the government’s countermeasures against emerging NPS, effectively reducing the dangerous influences on substances of abuse.新興影響精神物質管制藥品電腦模擬篩選卡西酮New Psychoactive Substancescontrolled substancesvirtual screeningcathinones