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題 名 | 神經影像學、多巴胺D2受體及抗精神病藥物=Neuroimaging, Dopamine D[feaf]Receptor, and Antipsychotics |
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作 者 | 蘇東平; | 書刊名 | 臺灣精神醫學 |
卷 期 | 12:3 1998.09[民87.09] |
頁 次 | 頁3-15 |
分類號 | 418.21 |
關鍵詞 | 多巴胺D2受體佔有率; 精神分裂症; 神經腦影象學; 典型及非典型抗精神病劑; Dopamine D[feaf]receptor occupancy; Schisophrenia neuroimaging; Typical and Atypical antipsychotics; |
語 文 | 中文(Chinese) |
中文摘要 | 神經腦影像學近幾年的快速發展對精神醫學的研究有重大影響。活體內 (in vivo)腦基底核dopamine二型(D2)受體之影像攝影提供了極重要的工具去檢驗D2受體的 被阻斷為抗精神病藥物作用機制-精神分裂病dopamine假說的理論基礎。本文選擇過去十 年來有關D2受體腦影像學之重要文獻作系統性的回顧,企圖了解D2受體佔有率和抗精神病劑 療效,及錐體外症候��(extrapyramidal side effect,EPS)之間的關係。並藉劑量,血清濃 度,和D2佔有率的曲直線或直線相關,引導我們做藥物選擇並減少副作用。典型抗精神病劑 如haloperidol以較低劑量即可達高度D2之佔有率。似乎需達到60-70%以上,療效才會出現 。然而超過此閾值不但療效未增加反而容易造成EPS。非典型藥物如clozapine其療效之佔有 率可從低度18%到極高度90%不等,然卻沒有EPS的出現。有趣的是,任何一種抗精神病劑非 要有對D2受體之阻斷(不管程度高或底),才能有療效出現,顯示非典型藥物可經D2受體以 外之神經傳導素如serotonin之機制來達成療效。這些研究結果不但在治療精神分裂症之用 藥劑量上產生直接的影響,而且使以dopamine為精神分裂症唯一的假設受嚴峻的挑戰。今後 的研究必須從抗精神病劑臨床作用的廣泛假設,重新檢視其基本藥理機轉,進而發明更新型 的藥物。最後,本文就研究方法可能會影響結果的因素作了詳細的剖析,並列出目前無法解 決的問題以作為日後研究方向的指針,包括作為參考標準的正常受試者,其D2受體密度有相 當個別差異性,內生性dopamine,放射性化合物(ligand)和抗精神病劑之間的交互作用以及 影像資料分析的計算方法(modeling strategies)。 |
英文摘要 | The ability to estimate the occupancy of dopamine D2 receptors in vivo with the use of functional brain imaging techniques utilizing radioligands has provided a critical tool for assessing the involvement of the D2 receptor in the mechanism of action of antipsychotic medication. In order to further clarify the relationship between imaging findings on D2 receptor occupancy and response to antipsychotic treatment and extrapyramidal symptoms (EPS), we reviewed the literatures over the past decade on D2 receptor imaging in positron emission tomography (PET) and single photon emission computed tomography (SPECT). A curvilinear or linear association between dose, blood level and D2 occupancy has been consistently reported and it has been clearly established that D2 receptor occupancy saturates gradually in patients treated with atypical antipsychotics, while a steep saturation occurs in the treatment with typical antipsychotics. All typical antipsychotics induce high levels of D2 occupancy at even low clinical doses. Therapeutic response is associated with an occupancy threshold of 60-70%. Increasing the degree of dopamine receptor blockade beyond this threshold range is probably not of therapecutic benefit, and seems to increase the risk of developing EPS. Clozapine, an atypical antipsychotic, achieves clinically therapeutic response with a wide range of D2 occupancies (18 to 90%) with a much lower risk of EPS than conventional agents. This finding indicates that factors other than D2 receptor occupancy may be predictive of relative antipsychotic efficacy but yet no drug with antipsychotic action has been identified which does not also have a significant affinity for the D2 receptor. These results of this area of research have had a direct impact on dosing practices in the management of schizophrenia and have also necessitated a reexamination of widespread clinical assumptions about the basic pharmacotherapeutic mechanisms of these drugs. Finally, the widespread inter-individual variation of D2 receptor densities in normal subjects, interaction of endogenous dopamine with ligand binding, and modeling strategies for analyzing scan data are associated with methodological confounds. (Full Text in Chinese) |
本系統中英文摘要資訊取自各篇刊載內容。